Wake Up! Resuscitation of Viable but Nonculturable Bacteria: Mechanism and Potential Application

Abstract

The viable but nonculturable (VBNC) state is a survival strategy for bacteria when encountered with unfavorable conditions. Under favorable environments such as nutrient supplementation, external stress elimination, or supplementation with resuscitation-promoting substances, bacteria will recover from the VBNC state, which is termed “resuscitation”. The resuscitation phenomenon is necessary for proof of VBNC existence, which has been confirmed in different ways to exclude the possibility of culturable-cell regrowth. The resuscitation of VBNC cells has been widely studied for the purpose of risk control of recovered pathogenic or spoilage bacteria. From another aspect, the resuscitation of functional bacteria can also be considered a promising field to explore. To support this point, the resuscitation mechanisms were comprehensively reviewed, which could provide the theoretical foundations for the application of resuscitated VBNC cells. In addition, the proposed applications, as well as the prospects for further applications of resuscitated VBNC bacteria in the food industry are discussed in this review.

1. Introduction

Since it was first discovered in Escherichia coli and Vibrio cholerae in 1982, the viable but nonculturable (VBNC) state has been a widely known phenomenon adopted by microorganisms when confronted with stressful environments [1]. Under this state, VBNC cells lose the ability to grow on routine culture medium, but their metabolic activities and gene expression capacities are retained, and the cytoplasmic membranes remain integrated [2]. However, this state is still controversial due to the suspicion that VBNC cells are actually “dying” cells with residuary metabolic activities that cannot be cultured on media, or that VBNC cells are “dead” cells with minor injuries on the membrane [3]. There are distinct differentiations between death and the VBNC state: bacterial death is the point where the injury extent is beyond the ability of a cell to resume growth; however, the VBNC state postulates a specific program of a long-term survival state rather than a short-term survival state followed by a further dead state [4]. In this circumstance, resuscitation is a keystone of the VBNC state. The resuscitation phenomenon from the VBNC state was first recognized in Salmonella enteritidis and E. coli in 1984 [5]. While providing VBNC bacteria with favorable conditions, the transition from a VBNC state to a culturable state is termed “resuscitation” [2]. Entry into the VBNC state can be considered as a survival strategy under stresses only when the VBNC cells possesses the ability to resuscitate. In other words, resuscitation is a requisite to prove the existence of the VBNC state [4].

VBNC bacteria are widely distributed in environments such as water, air, soil, foods, medical facilities, food processing procedures, and so on [1]. A large proportion of bacteria that can enter the VBNC state are pathogenic bacteria, which may still express toxins under the VBNC state or regain infectivity and pathogenicity after resuscitation, causing human illness or food spoilage [2,6]. The resuscitation of VBNC cells in foods may take place during shelf-life storage, which could be associated with foodborne outbreaks [7]. For a long time, researchers spent a lot of effort studying the risks of VBNC-state bacteria and resuscitated cells to human health. Makino et al. proved that VBNC E. coli O157:H7 in salted salmon roe could regain pathogenicity in germfree mice by resuscitating in the mouse intestine [8]; VBNC E. coli O157:H7 and VBNC Legionella pneumophila cells retained the ability to produce toxin genes or virulence proteins [9,10]; VBNC Campylobacter jejuni retained the ability to invade Caco-2 human intestinal epithelial cells in vitro [11]. Therefore, VBNC-state bacteria and, more importantly, their resuscitation, are becoming hot areas in food safety research. However, every coin has two sides. When functional bacteria enter the VBNC state, things could be different; the prevention and control of resuscitation sometimes may be switched to promotion and reasonable application, which may play key roles in ecological processes and/ or have great value in the food industry [12]. No matter for what reason, the exploration and recognition of resuscitation mechanisms is necessary and of great significance.

In this review, the different aspects of resuscitation including the confirmation strategies, resuscitation factors, resuscitation mechanisms, as well as the prospects for potential application in the food industry have been comprehensively reviewed. This review aims to provide updated and in-depth references for researchers and lay a foundation for investigations into the isolation and application of resuscitated VBNC bacteria.

2. Confirmation of Resuscitation from the VBNC State

Since the VBNC state is an ecologically significant state for bacteria, the ability of cells to undergo a resuscitation process from this dormant state to an actively metabolizing state must be possible to prove the existence of the VBNC state. There was skepticism that the regrowth phenomenon might be due to the very few culturable cells rather than the resuscitation of VBNC cells [13,14,15]. For example, Bogosian et al. thought that the resuscitation of VBNC-state V. vulnificus induced by a low temperature was the regrowth of H₂O₂ sensitive culturable cells [13]. To contradict the above suspicions, several strategies were adopted to exclude the impact of possibly existent culturable cells. For instance, the induced VBNC-state bacterial suspensions were diluted serially to minimize the possible existence of culturable cells before resuscitation [16,17]. When mixtures of culturable and nonculturable cells are diluted to the point where only nonculturable cells are present, the revived cells are resuscitated cells from the VBNC state [18]. In addition, antibiotics such as ampicillin were added to the medium after VBNC induction to inhibit the proliferation of remaining culturable cells, the actively growing cells during the resuscitation procedure were therefore confirmed to be resuscitated cells from the VBNC state [19]. Furthermore, the possibility of the regrowth of H₂O₂-sensitive culturable cells was excluded by the addition of an H₂O₂ scavenger including sodium pyruvates and catalases to the resuscitation medium [20,21]. Based on the above strategies, the resuscitation process from the VBNC state was confirmed and the strategies were further applied in resuscitation-related investigations. With the evidence proposed above, resuscitation is now widely accepted as the recovery of VBNC cells, which is usually determined through plate counting or turbidity measurement [6,22].

The ability to resuscitate is dependent on the persistent period of the VBNC state and external stress intensity. It was proposed that resuscitation ability was gradually impaired with a prolonged VBNC-state duration time [20,23]. After an overlong time, bacteria might even lose the ability to resuscitate [24]. Therefore, this period was defined as the “resuscitation window” [25]. In addition, Zhao et al. discovered that the resuscitation ability of VBNC state E. coli O157:H7 reduced significantly with an increased intensity of induction conditions [26].

3. Resuscitation: The Reverse Process of the VBNC State?

Plenty of factors are contributory to the resuscitation of VBNC cells, including, but not limited to, external stress removal, supplementation with peroxidases, coculturing with or being inoculated to the host of VBNC cells, and supplementation with resuscitation promoting factors (Rpfs) (Table 1). In many cases, the simple reversal of VBNC-inducing factors was sufficient to allow resuscitation, so the resuscitation process sometimes might be simply regarded as a reverse process of the VBNC state. However, it may be inexact because the removal of stressful environments sometimes may not be contributory to resuscitation [27]. In addition, other resuscitation factors such as Rpfs and autoinducers (AIs) have also implied the existence of signaling pathways to stimulate resuscitation. Therefore, the resuscitation process may be a complicated physiological process rather than the simple reverse of the VBNC sate.

VBNC cells have distinct characteristics such as declined metabolic activity, decreased or loss of pathogenicity, dwarfing, or abnormal morphology [25,28,29]. Stimulated by a variety of environmental, biological, or chemical stimuli, VBNC cells may resuscitate and recover their cell division ability with an elevated metabolic level, as well as pathogenicity and cell morphology (Figure 1). The recovery of the abnormal morphology of VBNC cells to some extent is a re-shape process, and the restored cell division ability during resuscitation from the VBNC state requires the re-synthesis of cytoplasmic proteins and cell wall peptidoglycan. Through supplementing chloramphenicol and penicillin, which inhibits protein and peptidoglycan synthesis, respectively, to the resuscitation medium, VBNC state V. vulnificus was found unable to resuscitate [24,30]. In addition, after the inhibition of the penicillin-binding proteins PBP1 and PBP5, which were involved in the late assembly of peptidoglycan, VBNC state E. Faecalis cells could not resuscitate [31]. Therefore, resuscitation is not simply a reverse process of the VBNC state; newly synthesized proteins and possibly a remodeling of the cell wall to shape a normal morphology may be necessary in this process.

Table 1

Conditions that facilitate the resuscitation process of VBNC cells.

Resuscitation Factors	Bacterial Species	Resuscitation Conditions		References
		VBNC-State Induction Condition	Corresponding Resuscitation Condition
External stress removal	Arcobacter butzleri, Aeromonas hydrophila, Staphylococcus aureus, Vibrio vulnificus, E. coli	Low temperature	Temperature up-shift	[24,32,33,34,35,36]
	Salmonella bovismorbificans, Enterococcus faecalis, Citrobacter sp., V. cholerae, Listeria monocytogenesisolates, Enterococci sp., Pasteurella piscicida, Yersinia pestis, V. shiloi, V. tasmaniensis, V. parahaemolyticus	Starvation	Addition of nutrients	[29,37,38,39,40,41,42,43,44,45]
	Enterobacter cloacae	Desiccation	Rewetting	[46]
	E. coli O157:H7, S. enterica serovar Typhimurium, L. monocytogenes	Low pH	Adjustment to the optimal pH	[47]
	Acetic acid bacteria, lactic acid bacteria	O2 deprivation	Addition of O2	[48]
	E. coli O104:H4, Acidovorax citrulli, Erwinia amylovorain	Copper	Addition of chelating agent	[49,50,51]
	S. enterica, E. coli O157:H7	Food processing techniques	Stress removal	[26,52]
Supplementation with peroxidases	Yeasts, Ralstonia solanacearum, E. coli O157:H7, Enterococcus sp., Salmonella sp. S. aureus, V. cincinnatiensis	Catalase, sodium pyruvate, SOD, GST, CAT, acetaldehyde		[53,54,55,56,57,58,59,60,61]
Host of VBNC cells	Legionella pneumophila, E. coli O157:H7, Campylobacter jejuni, Helicobacter pylori, L. monocytogenes, V. cholerae O1, Francisella tularensis, E. faecalis, Campylobacter sp.	Yolk sacs of embryonated eggs/1-week-old chicks, Caco-2 human intestinal epithelial cells, passage in the mouse intestine, co-culture with eukaryotic cells, injected intraperitoneally into mice, mice stomachs, co-culture with Acanthamoeba/Castellanii/Acanthamoeba polyphaga, ingestion by C. elegans, inoculated in iron-dextran-treated mice		[9,11,62,63,64,65,66,67,68,69,70,71,72,73,74,75,76,77,78,79]
Supplementation with substances that could promote resuscitation	Salmonella typhimurium, E. coli O157:H7, Vibrio sp., V. parahaemolyticus	Supplementation with autoinducer (AI)		[6,80,81,82]
	H. pylori, Mycobacterium tuberculosisare, Rhodococcus sp., actinobacteria, M. smegmatis, Sphingomonas and Pseudomonas, Rhodococcus biphenylivorans strain TG9T	Supplementation with resuscitation promoting factor (Rpf)		[83,84,85,86,87,88,89,90,91,92,93]

4. Mechanisms of Resuscitation

Previously, most VBNC-related studies focused on the exploration of formation mechanism [22,94,95,96], while studies on the mechanisms of resuscitation were rare. For the purpose of preventing and controlling the hidden risk caused by VBNC cells (resuscitated VBNC cells) or VBNC bacterial strain application after resuscitation, an explanation of the resuscitation mechanism was necessary. Summarized from the existing studies, such mechanisms can be classified into the following aspects: resuscitation promoting factors (Rpfs), quorum sensing, pyruvates sensing and application, and mechanisms based on global metabolism analysis.

4.1. Rpfs

The discovery and application of Rpf is a notable landmark in the resuscitation of VBNC cells. Rpf protein was first discovered in M. luteus as a bacterial cytokine, which promotes the resuscitation and growth of non-growing or dormant cells [97,98]. Rpf is a muralytic enzyme revealed by its cell wall peptidoglycan lysis ability, which contains a 70-residue domain at the C-terminal that adopts a lysozyme-like fold, and the invariant catalytic glutamate residue is conserved [99]. Similar proteins are widely occurred among other high G+C gram-positive bacteria, including corynebacterial, mycobacteria, streptomycetes, and fermicutes (contain Rpf analogues) [100]. It was reported that Rpf protein with a picomolar concentration could increase the viable cell number of dormant M. luteus at least 100-fold [98].

The resuscitation effect of Rpf was significant; however, its functioning mechanisms were not thoroughly studied. Through analyzing the products from mycobacterial peptidoglycan hydrolysis reactions, RpfB was found to form a complex with a protein named as resuscitation-promoting factor interacting protein (RipA) [101]. In this complex, RpfB cleaves the β-1,4-glycosidic bond between N-acetylmuramic acid (MurNAc) and GlcNAc, whereas RipA is predicted to be an endopeptidase that cleaves the stem peptide (D-iGlu-meso-diaminopimelic acid (Dap)) [101,102]. Both proteins colocalize at the septum of dividing cells and work synergistically to hydrolyze mycobacterial PG [103]. The complex of RpfB–RipA was reported to be inhibited by penicillin binding protein 1 (PBP1): RipA would form a complex with PBP1 and form a thick layer of PG at the septum. With the increased concentration of RpfB, RipA might exchange PBP1 for RpfB to form a new complex with a high efficiency of PG hydrolysis [104]. Some researchers thought that such a type of cell wall hydrolysis would directly stimulate VBNC cell resuscitation, since the peptide moieties of PG were crosslinked heavily in the VBNC state to resist external stresses [28,101,105]. Therefore, the recruitment of Rpf and RipA during PG remodeling is essential for cell division and resuscitation (Figure 2A). Apart from that, the PG fragments derived from cell wall hydrolysis could directly activate resuscitation [106]. However, how exactly PG fragments activate the resuscitation process remains unclear and researchers have proposed hypotheses to try to explain it. Panutdaporn et al. found that the addition of rabbit anti-Rpf Ab inhibited the resuscitation effect by Rpf, thereby suggesting that Rpf might be a signal molecule that could bind to the receptor to trigger the resuscitation process [107]. Moreover, the extracytoplasmic domain of Ser/Thr kinase PknB in Mycobacterium tuberculosis could bind exogenous PG fragments hydrolyzed by Rpf with its muralytic activity, which was conducive for PknB to localize at the mid-cell to stimulate growth [108] (Figure 2B). Although possible mechanisms have been proposed, more evidence is still needed to prove the activation process of PG fragments in resuscitation, which is a problem to be solved in future studies.

Other Rpf analogues were also reported to possess resuscitation-promoting abilities. The YeaZ protein in V. parahaemolyticus, V. harveyi, S. typhimurium, and E. coli has been shown to have promoting effects on VBNC-state recovery [107,109,110,111]. The yeaZ gene was found to be ubiquitous in the genome of bacteria such as Salmonella sp. and E. coli, which was necessary for bacterial growth [112]. Zhao et al. proposed that YeaZ exhibited protease activity, and muralytic activity was lower. Single amino acid mutation greatly affected protease activity, as well as resuscitation-promoting ability [113]. However, the impact of mutation was much less on the muralytic activity of YeaZ, and the resuscitation-promoting effect was not affected [113]. Hence, in contrast to Rpf, the promoting effect of YeaZ may be correlated with its protease activities, but its function mechanism lacks further investigation.

4.2. Quorum Sensing

Quorum sensing (QS) is a widespread communication system in bacteria, which is a type of population density-dependent cell–cell signaling that triggers changes in behavior when the bacterial population reaches a critical density [114]. QS signaling can result in global changes in gene expression [115]. Typically, signal molecules are continually generated with a low bacterial concentration, and the signal accumulates to a threshold concentration as the population density increases. Afterwards, the signal will interact with its receptor protein to cause a coordinated change in bacterial gene expression [115]. Such hormone-like molecules are termed as autoinducers (AI), of which there are several types, including acyl-homoserine lactone (AHL)-type signals (usually generated in G^- bacteria), short oligopeptide signals (in G⁺ bacteria), Streptomyces γ-butryolactones, and the AI-2 family (in V. harveyi and S. typhimurium) [114].

QS signaling in bacteria can orchestrate an adaption to stressful conditions, and it has been reported to play a role in the resuscitation of VBNC cells. Ayrapetyan et al. discovered that the bacterial cell-free supernatants of V. vulnificus containing AI-2 molecules could awake VBNC Vibrio populations within oysters and seawater, which was inhibited by the QS inhibitor cinnamaldehyde [A]. Previous studies have indicated that the QS system was involved in the activation of superoxide or catalase to regulate the antioxidation activities in Pseudomonas aeruginosa [116]. Furthermore, Liao et al. (2019) also suggested that the QS system triggered the expression of catalase to restore the growth of VBNC-state S. typhimurium [80]. In accordance with that, AI-2 was found to be useless in the resuscitation of the rpoS mutant of V. vulnificus, whose production of catalase was suppressed [82]. Hence, it was suggested that RpoS is also an important factor in AI-2-mediated resuscitation [82,117]. Based on the above results, a model was proposed (Figure 3): during resuscitation, the gradually generated AI-2 molecules synthesized by LuxS specifically bind to the periplasmic binding protein of LuxP, which forms a two-component sensing kinase system with LuxQ [118]. With a low level of AI-2, LuxQ acts as a kinase, but it acts as a phosphatase while AI-2 is at a high level. Therefore, the phosphorelay of LuxO derepresses the expression of LuxR (a transcription factor in the QS regulon), which can stimulate rpoS expression and subsequently induces the expression of catalase (KatG) [82]. Through this regulation, cells are allowed to persist under the toxic properties of H₂O₂ and revive to a culturable state [82]. To sum up, QS signaling may be critical for the resuscitation process of VBNC bacteria.

4.3. Pyruvates Sensing and Application

Sodium pyruvate (SP), a well-known intermediate key metabolite in glycolysis, is known to be functional in the resuscitation of VBNC cells. VBNC cells are able to grow on standard media, but they can revive on media supplemented with SP [26]. SP has long been regarded as an H₂O₂-degrading compound that could facilitate the resuscitation of VBNC cells under prolonged stress or the effects of toxic chemicals, such as H₂O₂ produced in a culture media during autoclaving [54,119,120,121]. It was suggested that VBNC cells could be resuscitated to a culturable state by SP or other substances such as catalase and superoxide dismutase, due to their H₂O₂- or reactive oxygen-degrading effect [20,21].

More opinions have emerged recently. Apart from being an H₂O₂-degrading compound, pyruvate is also a kind of carbon source that can be utilized by bacterial cells. Morishige et al. found that pyruvate and its analogue α-ketobutyrate both showed restoration activities; however, other well-known antioxidant or radical-scavenging reagents such as N-acetyl-L-cysteine, α-lipoate, and D-mannitol were ineffective in resuscitating VBNC Salmonella Enteritidis cells induced by H₂O₂ [57]. Through further investigation, it was implied that α-keto acids and pyruvate were incorporated by VBNC cells, which were related to the restoration of the biosynthesis of macromolecules, especially DNA, not just degrading intracellular peroxide [57]. It was later shown that pyruvate was avidly taken up by starved and cold-stressed VBNC E. coli cells through the high-affinity pyruvate/H⁺ symporter BstT/YhjX, which was regulated by two pyruvate-sensing hidtidine kinase response regulator systems, BtsS/BtsR and YpdA/YpdB, respectively [122]. BtsSR and YpdAB are two-component systems (TCSs) which respond to extracellular pyruvate, composed of a membrane-integrated histidine kinase (BtsS/YpdA) that can perceive pyruvate, and a cytoplasmic response regulator (BtsR/YpdB) mediates btsT expression [123,124]. With the import of pyruvate, cells then initiate DNA and protein biosynthesis for growth restoration (Figure 4). Therefore, VBNC cells may utilize pyruvate as an alternative carbon source and correspondingly fine-tune their transport capacities and metabolism for resuscitation.

4.4. Mechanisms Based on Global Metabolism Analysis

On most occasions, the reported studies on resuscitation mechanisms were based on the role of specific proteins or pathways, which may result in a less systematic and comprehensive investigation. With the extensive application of high-throughput sequencing technologies in biomolecular frontiers, more research based on omics analysis has emerged in the investigation of not only the VBNC-formation mechanism, but also the resuscitation mechanism.

Up to now, most omics studies on resuscitation from the VBNC state were conducted based on proteomics analysis. A thorough iTRAQ-based proteomic profile analysis of VBNC and resuscitating cells of the plant-pathogenic bacterium Acidovorax citrulli was reported, indicating that protein expression varied in the different resuscitation processes [125]. In the early stage, the proteins associated with carbon metabolism, degradation of naphthalene and aromatic compounds, and superoxide dismutase or catalase were significantly enriched, while the proteins involved in oxidative phosphorylation, bacterial chemotaxis, ABC transporting, and quorum sensing were significantly enriched at the late resuscitation stages [125]. From this point, it is evident that as the resuscitation progress proceeds, the metabolic activities may change to meet their different needs. In the early stage, heavily stressed bacterial cells try their best to cope with the adverse environments to guarantee their survival and gradually increase their metabolic activity for multiplication. With the increase in the cell number, cell-to-cell signaling is enhanced to better adapt the environment for further revival. The proteomic profile of the resuscitating V. parahaemolyticus was compared with the VBNC state and the exponential phase cells, revealing that the metabolic activity of resuscitated cells shared minor differences with exponential phase cells, but when compared with VBNC cells, the differently expressed cells were comprehensively upregulated, which mainly involved protein synthesis, secretion system, trans-membrane transport, adhesion, movement, and other vital processes [126]. Debnath et al. suggested that the most variably expressed proteins of resuscitating V. cholerae showed a combination mode of adaptive and survival responses under conditions of nutrient limitation [127]. For example, the expression of PhoX, PstB, and Xds might help in the utilization of extracellular DNA to promote growth; the expression of AhpC addressed the significance of the oxidative stress response; the upregulation of EctC, an enzyme related to the biosynthesis of ectoine that is crucial for osmoadaptation, might be a response to the long-term stress of high salinity [127]. The analysis of global metabolism provides an overall perspective of the resuscitation mechanisms, which can also be a basic foundation for further investigation of specific mechanisms.

5. Potential Application of the Resuscitation of VBNC Cells

Unculturable microorganisms exist as “dark matter” in ecological environments, which greatly affects the exploration and utilization of microbial resources. This unculturability is largely derived from the adverse natural habitat conditions of bacteria, since they are always inconstant, and their inherent characteristics such as the oligotrophy of water, desiccation of soil, and existence of pollutants greatly limit the normal growth of bacteria, many of which are functional species. Therefore, resuscitating VBNC bacteria could provide huge candidates for obtaining high-value strains.

At present, the resuscitation of VBNC bacteria has been proved to be effective in shaping bacteria populations. With the resuscitation-promoting ability of the Rpf protein, the abundance of specific taxa was significantly increased and 51 potentially novel bacterial species were isolated from a nutrient-rich compost soil [128]. Su et al. also reported that after resuscitation by Rpf, bacterial diversity was increased, especially in terms of functional bacterial communities [91]. Since then, more studies have emerged on resuscitating VBNC bacteria to search functional bacteria populations in samples of soil or water. Wang et al. obtained a richer species diversity while resuscitating cells with Rpf protein, and two rare actinobacteria were resuscitated and isolated [129]. It was proposed that resuscitating VBNC bacteria through adding Rpf into polychlorinated biphenyl-contaminated soil accelerated the biodegradation of Aroclor 1242, which was mainly due to the resuscitation of key bio-degraders of the Sphingomonas and Pseudomonas genera [89]. In addition, bacterial populations were shaped, and 13 strains were resuscitated and isolated from river sediments under the function of Rpf, which possessed nitrogen removal capacities [92]. Therefore, through resuscitating VBNC cells, environmental-friendly strains that possess pollution control capacities were separated for further use, whose effect was notable. The resuscitating effect was achieved through the functioning of the Rpf protein. However, the Rpf protein is mainly derived from the culture supernatants of Micrococcus luteus or the heterologous expression of the Micrococcus luteus gene [83,91,130]. Other species may also express Rpf protein and have a significant resuscitation effect, and this area is therefore worth further exploration.

The resuscitation and separation of VBNC cells in foods seems meaningful in another aspect as well. For example, in fermentative foods, the lowered pH, lack of oxygen, and particular metabolites may pose negative impacts on the normal growth of bacteria, and some of them may enter the VBNC state. The resuscitation of the VBNC-state functional strains such as flavor-producing strains, fermentation strains, and probiotics, through adding resuscitation-promoting stimuli, is of great significance, and can be a research aspect in the future (Figure 5). Therefore, inspired by the Rpf-induced resuscitation, the application of VBNC-cell resuscitation may be conducted from two aspects. Except for with Rpf, more resuscitation-promoting conditions can be used in the resuscitation of bacteria in the VBNC state; in real food or other samples, bacterial strains can be separated and identified to search strains with the rpf gene (or Rpf protein), so that the strains could be adopted to increase microbial diversity in the samples, through which the source of the Rpf protein can be enriched.

6. Conclusions

The formation of VBNC-state pathogenic bacteria is a great threat to food safety and public health. However, when it comes to functional bacteria, entering a VBNC state makes them become a hidden resource for potential industrial application. In this article, aspects of the resuscitation of VBNC cells, including the definition and confirmation of resuscitation, promoting factors, and the mechanisms of resuscitation, are thoroughly reviewed, which could lay a firm theoretical foundation for the isolation and application of VBNC-state functional populations, as well as the prevention of risks arising from VBNC-state pathogenic bacteria. Attempts to resuscitate VBNC bacteria and the specific roles of the resuscitated cells have been studied in various environments in recent years, the effects of which have been proved to be profound. However, such studies in the food area are rare. Regarding the universality of the emergence of the VBNC phenomenon in the food industry, waking up the dormant and functional population may provide a new approach to obtaining valuable microbial resources, which may have great value for the food industry. However, care should be taken regarding the corresponding concerns. The microbial communities in food products, especially in fermented foods, are always complicated, and whether the resuscitation process restores some “unfavorable” microorganisms at the same time is unknown. Therefore, we think that the resuscitation of VBNC cells may be beneficial for the isolation of rare species or functional populations from foods, but the direct supplementation of resuscitation-promoting substances into foods should be rigorously evaluated to avoid the occurrence of food safety events and serious alterations to foods.

Author Contributions

Conceptualization, H.P.; Writing—Original Draft Preparation, H.P.; Writing—Review and Editing, Q.R.; Funding Acquisition, H.P. All authors have read and agreed to the published version of the manuscript.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

This review did not report any data.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

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Figures and Table

Figure 1. The formation of the VBNC state and its resuscitation. While confronted with prolonged stressful environments, a small proportion of viable bacteria will enter the VBNC state, under which bacteria cannot develop into colonies on their culture medium, but cellular metabolic activities are retained although significantly decreased. When provided with favorable conditions, VBNC cells will resuscitate to the viable state with recovered metabolic activity and culturability.

Figure 2. Function mechanisms of Rpf protein. (A) Rpf and RipA work synergistically to remodel the cell wall to promote cell division and resuscitation. (B) Cell wall fragments digested by Rpf and RipA serve as signaling molecules binding with a receptor to trigger resuscitation related pathways.

Figure 3. Generalized schematic of the effect of the QS phosphorelay system on the resuscitation of VBNC bacteria. The thin arrows mean promotion effects, and the thick arrow means transportation direction of AI-2.

Figure 4. The uptake and utilization of pyruvate to resuscitate VBNC bacteria. Pyruvate was taken up through the high-affinity pyruvate/H+ symporter BstT/YhjX, which was regulated by two pyruvate-sensing hidtidine kinase response regulator systems, BtsS/BtsR and YpdA/YpdB, respectively. BtsSR and YpdAB are two-component systems which respond to extracellular pyruvate, composed of a membrane-integrated histidine kinase (BtsS/YpdA) that can perceive pyruvate, and a cytoplasmic response regulator (BtsR/YpdB) mediates btsT expression. With the import of pyruvate, cells then initiate DNA and protein biosynthesis for growth restoration. The black thin arrows indicate that the proteins/substances promote the synthesize of the transporter of BtsT/YhjX. The grey thick arrows mean the promotion effect of pyruvate to resuscitation through biosynthesis of macromolecules. The black thick arrows mean promotion effect of pyruvate to resuscitation through removing H2O2.

Figure 5. Assumption of VBNC bacteria resuscitation to separate novel species for application in the food industry.

References

1. Dong, K.; Pan, H.; Yang, D.; Rao, L.; Zhao, L.; Wang, Y.; Liao, X. Induction, detection, formation, and resuscitation of viable but non-culturable state microorganisms. Compr. Rev. Food Sci. Food Saf.; 2020; 19, pp. 149-183. [DOI: https://dx.doi.org/10.1111/1541-4337.12513]

2. Oliver, J.D. The viable but nonculturable state in bacteria. J. Microbiol.; 2005; 43, pp. 93-100. [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15765062]

3. Trevors, J.T. Can dead bacterial cells be defined and are genes expressed after cell death?. J. Microbiol. Methods; 2012; 90, pp. 25-28. [DOI: https://dx.doi.org/10.1016/j.mimet.2012.04.004]

4. Bogosian, G.; Bourneuf, E.V. A matter of bacterial life and death. EMBO Rep.; 2001; 2, pp. 770-774. [DOI: https://dx.doi.org/10.1093/embo-reports/kve182] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11559589]

5. Roszak, D.B.; Grimes, D.J.; Colwell, R.R. Viable but nonrecoverable stage of Salmonella enteritidis in aquatic systems. Can. J. Microbiol.; 1984; 30, pp. 334-338. [DOI: https://dx.doi.org/10.1139/m84-049] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/6372975]

6. Yoon, J.H.; Bae, Y.M.; Jo, S.; Moon, S.K.; Oh, S.W.; Lee, S.Y. Optimization of resuscitation-promoting broths for the revival of Vibrio parahaemolyticus from a viable but nonculturable state. Food Sci. Biotechnol.; 2021; 30, pp. 159-169. [DOI: https://dx.doi.org/10.1007/s10068-020-00843-2] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/33552627]

7. Ferro, S.; Amorico, T.; Deo, P. Role of food sanitising treatments in inducing the ‘viable but nonculturable’ state of microorganisms. Food Control; 2018; 91, pp. 321-329. [DOI: https://dx.doi.org/10.1016/j.foodcont.2018.04.016]

8. Makino, S.I.; Kii, T.; Asakura, H.; Shirahata, T.; Ikeda, T.; Takeshi, K.; Itoh, K. Does enterohemorrhagic Escherichia coli O157:H7 enter the viable but nonculturable state in salted salmon roe?. Appl. Environ. Microbiol.; 2000; 66, pp. 5536-5539. [DOI: https://dx.doi.org/10.1128/AEM.66.12.5536-5539.2000]

9. Alleron, L.; Khemiri, A.; Koubar, M.; Lacombe, C.; Coquet, L.; Cosette, P.; Jouenne, T.; Frere, J. VBNC Legionella pneumophila cells are still able to produce virulence proteins. Water Res.; 2013; 47, pp. 6606-6617. [DOI: https://dx.doi.org/10.1016/j.watres.2013.08.032]

10. Liu, Y.; Wang, C.; Tyrrell, G.; Li, X.F. Production of Shiga-like toxins in viable but nonculturable Escherichia coli O157:H7. Water Res.; 2010; 44, pp. 711-718. [DOI: https://dx.doi.org/10.1016/j.watres.2009.10.005]

11. Chaisowwong, W.; Kusumoto, A.; Hashimoto, M.; Harada, T.; Maklon, K.; Kawamoto, K. Physiological characterization of Campylobacter jejuni under cold stresses conditions, its potential for public threat. J. Vet. Med. Sci.; 2012; 74, pp. 43-50. [DOI: https://dx.doi.org/10.1292/jvms.11-0305]

12. Zhang, X.; Ahmad, W.; Zhu, X.; Chen, J.; Austion, B. Viable but nonculturable bacteria and their resuscitation: Implications for cultivating uncultured marine microorganisms. Mar. Life Sci. Technol.; 2021; 3, pp. 189-203. [DOI: https://dx.doi.org/10.1007/s42995-020-00041-3]

13. Bogosian, G.; Aardema, N.D.; Bourneuf, E.V.; Morris, P.J.; O’Neil, J.P. Recovery of hydrogen peroxide-sensitive culturable cells of Vibrio vulnificus gives the appearance of resuscitation from a viable but nonculturable state. J. Bacteriol.; 2000; 182, pp. 5070-5075. [DOI: https://dx.doi.org/10.1128/JB.182.18.5070-5075.2000]

14. Kong, I.-S.; Bates, T.C.; Hulsmann, A.; Hassan, H.; Smith, B.E.; Oliver, J.D. Role of catalase and oxyR in the viable but nonculturable state of Vibrio vulnificus. FEMS Microbiol. Ecol.; 2004; 50, pp. 133-142. [DOI: https://dx.doi.org/10.1016/j.femsec.2004.06.004] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19712354]

15. Ravel, J.; Knight, I.T.; Monahan, C.E.; Hill, R.T.; Colwell, R.R. Temperature-induced recovery of Vibrio cholerae from the viable but nonculturable state: Growth or resuscitation?. Microbiology; 1995; 141, pp. 377-383. [DOI: https://dx.doi.org/10.1099/13500872-141-2-377]

16. Ordax, M.; Marco-Noales, E.; Lopez, M.M.; Biosca, E.G. Survival strategy of Erwinia amylovora against copper: Induction of the viable-but-nonculturable state. Appl. Environ. Microbiol.; 2006; 72, pp. 3482-3488. [DOI: https://dx.doi.org/10.1128/AEM.72.5.3482-3488.2006]

17. Whitesides, M.D.; Oliver, J.D. Resuscitation of Vibrio vulnificus from the viable but nonculturable state. Appl. Environ. Microbiol.; 1997; 63, pp. 1002-1005. [DOI: https://dx.doi.org/10.1128/aem.63.3.1002-1005.1997] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16535534]

18. Puspita, I.D.; Kitagawa, W.; Kamagata, Y.; Tanaka, M.; Nakatsu, C.H. Increase in bacterial colony formation from a permafrost ice wedge dosed with a tomitella biformata recombinant resuscitation-promoting factor protein. Microbes Environ.; 2015; 30, pp. 151-156. [DOI: https://dx.doi.org/10.1264/jsme2.ME14119] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25843055]

19. Basaglia, M.; Povolo, S.; Casella, S. Resuscitation of viable but not culturable Sinorhizobium meliloti 41 pRP4-luc: Effects of oxygen and host plant. Curr. Microbiol.; 2007; 54, pp. 167-174. [DOI: https://dx.doi.org/10.1007/s00284-005-0482-3]

20. Boaretti, M.; Lleo, M.D.M.; Bonato, B.; Signoretto, C.; Canepari, P. Involvement of rpoS in the survival of Escherichia coli in the viable but non-culturable state. Environ. Microbiol.; 2003; 5, pp. 986-996. [DOI: https://dx.doi.org/10.1046/j.1462-2920.2003.00497.x]

21. Gupte, A.R.; de Rezende, C.L.E.; Joseph, S.W. Induction and resuscitation of viable but nonculturable Salmonella enterica Serovar Typhimurium DT104. Appl. Environ. Microbiol.; 2003; 69, pp. 6669-6675. [DOI: https://dx.doi.org/10.1128/AEM.69.11.6669-6675.2003]

22. Yang, D.; Wang, Y.; Zhao, L.; Rao, L.; Liao, X. Extracellular pH decline introduced by high pressure carbon dioxide is a main factor inducing bacteria to enter viable but non-culturable state. Food Res. Int.; 2022; 151, 110895. [DOI: https://dx.doi.org/10.1016/j.foodres.2021.110895] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/34980417]

23. Weichart, D.; McDougald, D.; Jacobs, D.; Kjelleberg, S. In situ analysis of nucleic acids in cold-induced nonculturable Vibrio vulnificus. Appl. Environ. Microbiol.; 1997; 63, pp. 2754-2758. [DOI: https://dx.doi.org/10.1128/aem.63.7.2754-2758.1997] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/9212422]

24. Masmoudi, S.; Denis, M.; Maalej, S. Inactivation of the gene katA or sodA affects the transient entry into the viable but non-culturable response of Staphylococcus aureus in natural seawater at low temperature. Mar. Pollut. Bull.; 2010; 60, pp. 2209-2214. [DOI: https://dx.doi.org/10.1016/j.marpolbul.2010.08.017] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20833402]

25. Pinto, D.; Santos, M.A.; Chambel, L. Thirty years of viable but nonculturable state research: Unsolved molecular mechanisms. Crit. Rev. Microbiol.; 2013; 41, pp. 61-76. [DOI: https://dx.doi.org/10.3109/1040841X.2013.794127] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23848175]

26. Zhao, F.; Bi, X.; Hao, Y.; Liao, X. Induction of viable but nonculturable Escherichia coli O157:H7 by high pressure CO₂ and its characteristics. PLoS ONE; 2013; 8, e62388. [DOI: https://dx.doi.org/10.1371/journal.pone.0062388] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23626816]

27. Weichart, D.; Kjelleberg, S. Stress resistance and recovery potential of culturable and viable but nonculturable cells of Vibrio vulnificus. Microbiology; 1996; 142, pp. 845-853. [DOI: https://dx.doi.org/10.1099/00221287-142-4-845] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8936311]

28. Signoretto, C.; Lleo, M.; Canepari, P. Modification of the peptidoglycan of Escherichia coli in the viable but nonculturable state. Curr. Microbiol.; 2002; 44, pp. 125-131. [DOI: https://dx.doi.org/10.1007/s00284-001-0062-0]

29. Yoon, J.H.; Lee, S.Y. Characteristics of viable-but-nonculturable Vibrio parahaemolyticus induced by nutrient-deficiency at cold temperature. Crit. Rev. Food Sci. Nutr.; 2019; 60, pp. 1302-1320. [DOI: https://dx.doi.org/10.1080/10408398.2019.1570076]

30. Nilsson, L.; Oliver, J.D.; Kjelleberg, S. Resuscitation of Vibrio vulnificus from the viable but nonculturable state. J. Bacteriol.; 1991; 173, pp. 5054-5059. [DOI: https://dx.doi.org/10.1128/jb.173.16.5054-5059.1991]

31. del Mar Lleò, M.; Benedetti, D.; Tafi, M.C.; Signoretto, C.; Canepari, P. Inhibition of the resuscitation from the viable but non-culturable state in Enterococcus faecalis. Environ. Microbiol.; 2007; 9, pp. 2313-2320. [DOI: https://dx.doi.org/10.1111/j.1462-2920.2007.01345.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17686027]

32. Fera, M.T.; Maugeri, T.L.; Gugliandolo, C.; la Camera, E.; Lentini, V.; Favaloro, A.; Bonanno, D.; Carbone, M. Induction and resuscitation of viable nonculturable Arcobacter butzleri cells. Appl. Environ. Microbiol.; 2008; 74, pp. 3266-3268. [DOI: https://dx.doi.org/10.1128/AEM.00059-08] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18378639]

33. Maalej, S.; Gdoura, R.; Dukan, S.; Hammami, A.; Bouain, A. Maintenance of pathogenicity during entry into and resuscitation from viable but nonculturable state in Aeromonas hydrophila exposed to natural seawater at low temperature. J. Appl. Microbiol.; 2004; 97, pp. 557-565. [DOI: https://dx.doi.org/10.1111/j.1365-2672.2004.02336.x]

34. Nowakowska, J.; Oliver, J.D. Resistance to environmental stresses by Vibrio vulnificus in the viable but nonculturable state. FEMS Microbiol. Ecol.; 2013; 84, pp. 213-222. [DOI: https://dx.doi.org/10.1111/1574-6941.12052] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23228034]

35. Rao, N.V.; Shashidhar, R.; Bandekar, J.R. Induction, resuscitation and quantitative real-time polymerase chain reaction analyses of viable but nonculturable Vibrio vulnificus in artificial sea water. World J. Microbiol. Biotechnol.; 2014; 30, pp. 2205-2212. [DOI: https://dx.doi.org/10.1007/s11274-014-1640-1] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24696138]

36. Zhang, S.; Ye, C.; Lin, H.; Lv, L.; Yu, X. UV disinfection induces a VBNC state in Escherichia coli and Pseudomonas aeruginosa. Environ. Sci. Technol.; 2015; 49, pp. 1721-1728. [DOI: https://dx.doi.org/10.1021/es505211e]

37. Ben Abdallah, F.; Lagha, R.; Bakhrouf, A. Resuscitation and morphological alterations of Salmonella bovismorbificans cells under starvation in soil. World J. Microbiol. Biotechnol.; 2007; 24, pp. 1507-1512. [DOI: https://dx.doi.org/10.1007/s11274-007-9633-y]

38. del Mar Lleo, M.; Tafi, M.C.; Canepari, P. Nonculturable Enterococcus faecalis cells are metabolically active and capable of resuming active growth. Syst. Appl. Microbiol.; 1998; 21, pp. 333-339. [DOI: https://dx.doi.org/10.1016/S0723-2020(98)80041-6]

39. Dhiaf, A.; Bakhrouf, A.; Witzel, K.P. Resuscitation of eleven-year VBNC Citrobacter. J. Water Health; 2008; 6, 565. [DOI: https://dx.doi.org/10.2166/wh.2008.131]

40. Fernández-Delgado, M.; García-Amado, M.A.; Contreras, M.; Incani, R.N.; Chirinos, H.; Rojas, H.; Suárez, P. Survival, induction and resuscitation of Vibrio cholerae from the viable but non-culturable state in the Southern Caribbean Sea. Rev. Inst. Med. Trop. Sao Paulo; 2015; 57, pp. 21-26. [DOI: https://dx.doi.org/10.1590/S0036-46652015000100003]

41. Lindbäck, T.; Rottenberg, M.E.; Roche, S.M.; Rørvik, L.M. The ability to enter into an avirulent viable but non-culturable (VBNC) form is widespread among Listeria monocytogenesisolates from salmon, patients and environment. Vet. Res.; 2009; 41, 08. [DOI: https://dx.doi.org/10.1051/vetres/2009056]

42. Lleò, M.; Bonato, B.; Signoretto, C.; Canepari, P. Vancomycin resistance is maintained in enterococci in the viable but nonculturable state and after division is resumed. Antimicrob. Agents Chemother.; 2003; 47, pp. 1154-1156. [DOI: https://dx.doi.org/10.1128/AAC.47.3.1154-1156.2003] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12604561]

43. Magarinos, B.; Romalde, J.; Cid, A.; Toranzo, A. Viability of starved Pasteurella piscicida in seawater monitored by flow cytometry and the effect of antibiotics on its resuscitation. Lett. Appl. Microbiol.; 1997; 24, pp. 122-126. [DOI: https://dx.doi.org/10.1046/j.1472-765X.1997.00366.x]

44. Pawlowski, D.R.; Metzger, D.J.; Raslawsky, A.; Howlett, A.; Siebert, G.; Karalus, R.J.; Garrett, S.; Whitehouse, A.C. Entry of Yersinia pestis into the viable but nonculturable state in a low-temperature tap water microcosm. PLoS ONE; 2011; 6, e17585. [DOI: https://dx.doi.org/10.1371/journal.pone.0017585] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/21436885]

45. Vattakaven, T.; Bond, P.; Bradley, G.; Munn, C.B. Differential effects of temperature and starvation on induction of the viable-but-nonculturable state in the coral pathogens Vibrio shiloi and Vibrio tasmaniensis. Appl. Environ. Microbiol.; 2006; 72, pp. 6508-6513. [DOI: https://dx.doi.org/10.1128/AEM.00798-06] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/17021199]

46. Pedersen, J.C.; Jacobsen, C.S. Fate of Enterobacter cloacae JP120 and Alcaligenes eutrophus AEO106(pRO101) in soil during water stress: Effects on culturability and viability. Appl. Environ. Microbiol.; 1993; 59, pp. 1560-1564. [DOI: https://dx.doi.org/10.1128/aem.59.5.1560-1564.1993] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/8517752]

47. Nicolò, M.S.; Gioffrè, A.; Carnazza, S.; Platania, G.; Silvestro, I.D.; Guglielmino, S.P.P. Viable but nonculturable state of foodborne pathogens in grapefruit juice: A study of laboratory. Foodborne Pathog. Dis.; 2011; 8, pp. 11-17. [DOI: https://dx.doi.org/10.1089/fpd.2009.0491] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20932087]

48. Millet, V.; Lonvaud-Funel, A. The viable but non-culturable state of wine micro-organisms during storage. Lett. Appl. Microbiol.; 2000; 30, pp. 136-141. [DOI: https://dx.doi.org/10.1046/j.1472-765x.2000.00684.x]

49. Aurass, P.; Prager, R.; Flieger, A. EHEC/EAEC O104:H4 strain linked with the 2011 German outbreak of haemolytic uremic syndrome enters into the viable but non-culturable state in response to various stresses and resuscitates upon stress relief. Environ. Microbiol.; 2011; 13, pp. 3139-3148. [DOI: https://dx.doi.org/10.1111/j.1462-2920.2011.02604.x]

50. Kan, Y.; Jiang, N.; Xu, X.; Lyu, Q.; Gopalakrishnan, V.; Walcott, R.; Burdman, S.; Li, J.; Luo, L. 2019. Induction and resuscitation of the viable but non-culturable (VBNC) state in Acidovorax citrulli, the causal agent of bacterial fruit blotch of cucurbitaceous crops. Front. Microbiol.; 2019; 10, 1081. [DOI: https://dx.doi.org/10.3389/fmicb.2019.01081]

51. Ordax, M.; Biosca, E.G.; Wimalajeewa, S.C.; López, M.M.; Marco-Noales, E. Survival of Erwinia amylovorain mature apple fruit calyces through the viable but nonculturable (VBNC) state. J. Appl. Microbiol.; 2009; 107, pp. 106-116. [DOI: https://dx.doi.org/10.1111/j.1365-2672.2009.04187.x]

52. Purevdorj-Gage, L.; Nixon, B.; Bodine, K.; Xu, Q.; Doerrler, W.T. Differential effect of food sanitizers on formation of viable but nonculturable Salmonella enterica in poultry. J. Food Prot.; 2018; 81, pp. 386-393. [DOI: https://dx.doi.org/10.4315/0362-028X.JFP-17-335]

53. Divol, B.; Lonvaud-Funel, A. Evidence for viable but nonculturable yeasts in botrytis-affected wine. J. Appl. Microbiol.; 2005; 99, pp. 85-93. [DOI: https://dx.doi.org/10.1111/j.1365-2672.2005.02578.x]

54. Imazaki, I.; Nakaho, K. Temperature-upshift-mediated revival from the sodium-pyruvate-recoverable viable but nonculturable state induced by low temperature in Ralstonia solanacearum: Linear regression analysis. J. Gen. Plant Pathol.; 2009; 75, pp. 213-226. [DOI: https://dx.doi.org/10.1007/s10327-009-0166-0]

55. Kolling, G.L.; Matthews, K.R. Examination of recovery in vitro and in vivo of nonculturable Escherichia coli O157: H7. Appl. Environ. Microbiol.; 2001; 67, pp. 3928-3933. [DOI: https://dx.doi.org/10.1128/AEM.67.9.3928-3933.2001]

56. Lleo, M.M.; Bonato, B.; Tafi, M.C.; Signoretto, C.; Boaretti, M.; Canepari, P. Resuscitation rate in different enterococcal species in the viable but non-culturable state. J. Appl. Microbiol.; 2001; 91, pp. 1095-1102. [DOI: https://dx.doi.org/10.1046/j.1365-2672.2001.01476.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/11851818]

57. Morishige, Y.; Fujimori, K.; Amano, F. Differential resuscitative effect of pyruvate and its analogues on VBNC (viable but non-culturable) Salmonella. Microbes Environ.; 2013; 28, pp. 180-186. [DOI: https://dx.doi.org/10.1264/jsme2.ME12174] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23595023]

58. Morishige, Y.; Koike, A.; Tamura-Ueyama, A.; Amano, F. Induction of viable but nonculturable salmonella in exponentially grown cells by exposure to a low-humidity environment and their resuscitation by catalase. J. Food Prot.; 2017; 80, pp. 288-294. [DOI: https://dx.doi.org/10.4315/0362-028X.JFP-16-183]

59. Pasquaroli, S.; Zandri, G.; Vignaroli, C.; Vuotto, C.; Donelli, G.; Biavasco, F. Antibiotic pressure can induce the viable but non-culturable state in Staphylococcus aureus growing in biofilms. J. Antimicrob. Chemother.; 2013; 68, pp. 1812-1817. [DOI: https://dx.doi.org/10.1093/jac/dkt086] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23515246]

60. Yang, C.H.; Kong, H.G.; Bae, J.Y.; Lee, H.J.; Joo, H.J.; Jung, E.J.; Chung, E.; Lee, S.W. Induction of the viable but nonculturable state of Ralstonia solanacearum by low temperature in the soil microcosm and its resuscitation by Catalase. PLoS ONE; 2014; 9, e109792.

61. Zhong, L.; Chen, J.; Zhang, X.; Jiang, Y. Entry of Vibrio cincinnatiensis into viable but nonculturable state and its resuscitation. Lett. Appl. Microbiol.; 2009; 48, pp. 247-252. [DOI: https://dx.doi.org/10.1111/j.1472-765X.2008.02522.x]

62. Alleron, L.; Merlet, N.; Lacombe, C.; Frère, J. Long-term survival of Legionella pneumophila in the viable but nonculturable state after monochloramine treatment. Curr. Microbiol.; 2008; 57, pp. 497-502. [DOI: https://dx.doi.org/10.1007/s00284-008-9275-9]

63. Asakura, H.; Igimi, S.; Kawamoto, K.; Yamamoto, S.; Makino, S. Role of in vivo passage on the environmental adaptation of enterohemorrhagic Escherichia coli O157:H7: Cross-induction of the viable but nonculturable state by osmotic and oxidative stresses. FEMS Microbiol. Lett.; 2005; 253, pp. 243-249. [DOI: https://dx.doi.org/10.1016/j.femsle.2005.09.039]

64. Baffone, W.; Casaroli, A.; Citterio, B.; Pierfelici, L.; Campana, R.; Vittoria, E.; Guaglianone, E.; Donelli, G. Campylobacter jejuni loss of culturability in aqueous microcosms and ability to resuscitate in a mouse model. Int. J. Food Microbiol.; 2006; 107, pp. 83-91. [DOI: https://dx.doi.org/10.1016/j.ijfoodmicro.2005.08.015] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16290304]

65. Boehnke, K.F.; Eaton, K.A.; Fontaine, C.; Brewster, R.; Wu, J.; Eisenberg, J.N.S.; Valdivieso, M.; Baker, L.H.; Xi, C. Reduced infectivity of waterborne viable but nonculturable Helicobacter pylori strain SS1 in mice. Helicobacter; 2017; 22, e12391. [DOI: https://dx.doi.org/10.1111/hel.12391] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28436616]

66. Cappelier, J.; Minet, J.; Magras, C.; Colwell, R.; Federighi, M. Recovery in embryonated eggs of viable but nonculturable Campylobacter jejuni cells and maintenance of ability to adhere to HeLa cells after resuscitation. Appl. Environ. Microbiol.; 1999; 65, pp. 5154-5157. [DOI: https://dx.doi.org/10.1128/AEM.65.11.5154-5157.1999]

67. Cappelier, J.M.; Besnard, V.; Roche, S.; Garrec, N.; Zundel, E.; Velge, P.; Federighi, M. Avirulence of viable but non-culturable Listeria monocytogenes cells demonstrated by in vitro and in vivo models. Vet. Res.; 2005; 36, pp. 589-599. [DOI: https://dx.doi.org/10.1051/vetres:2005018] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15955283]

68. Cappelier, J.M.; Besnard, V.; Roche, S.M.; Velge, P.; Federigh, M. Avirulent viable but non culturable cells of Listeria monocytogenes need the presence of an embryo to be recovered in egg yolk and regain virulence after recovery. Vet. Res.; 2007; 38, pp. 573-583. [DOI: https://dx.doi.org/10.1051/vetres:2007017]

69. Colwell, R.; Brayton, P.; Herrington, D.; Tall, B.; Huq, A.; Levine, M. Viable but non-culturable Vibrio cholerae O1 revert to a cultivable state in the human intestine. World J. Microbiol. Biotechnol.; 1996; 12, pp. 28-31. [DOI: https://dx.doi.org/10.1007/BF00327795]

70. Epalle, T.; Girardot, F.; Allegra, S.; Maurice-Blanc, C.; Garraud, O.; Riffard, S. Viable but not culturable forms of Legionella pneumophila generated after heat shock treatment are infectious for macrophage-like and alveolar epithelial cells after resuscitation on Acanthamoeba polyphaga. Microb. Ecol.; 2014; 69, pp. 215-224. [DOI: https://dx.doi.org/10.1007/s00248-014-0470-x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25074793]

71. Forsman, M.; Henningson, E.W.; Larsson, E.; Johansson, T.; Sandström, G. Francisella tularensis does not manifest virulence in viable but non-culturable state. FEMS Microbiol. Ecol.; 2000; 31, pp. 217-224. [DOI: https://dx.doi.org/10.1111/j.1574-6941.2000.tb00686.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10719202]

72. García, M.T.; Jones, S.; Pelaz, C.; Millar, R.D.; Kwaik, Y.A. Acanthamoeba polyphaga resuscitates viable non-culturable Legionella pneumophila after disinfection. Environ. Microbiol.; 2007; 9, pp. 1267-1277. [DOI: https://dx.doi.org/10.1111/j.1462-2920.2007.01245.x]

73. Highmore, C.J.; Warner, J.C.; Rothwell, S.D.; Wilks, S.A.; Keevil, C.W. Viable-but-nonculturable Listeria monocytogenes and Salmonella enterica serovar Thompson induced by chlorine stress remain infectious. mBio; 2018; 9, e00540-e18. [DOI: https://dx.doi.org/10.1128/mBio.00540-18] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29666286]

74. Klančnik, A.; Guzej, B.; Jamnik, P.; Vučković, D.; Abram, M.; Možina, S.S. Stress response and pathogenic potential of Campylobacter jejuni cells exposed to starvation. Res. Microbiol.; 2009; 160, pp. 345-352. [DOI: https://dx.doi.org/10.1016/j.resmic.2009.05.002]

75. Mustapha, P.; Epalle, T.; Allegra, S.; Girardot, F.; Garraud, O.; Riffard, S. Monitoring of Legionella pneumophila viability after chlorine dioxide treatment using flow cytometry. Res. Microbiol.; 2015; 166, pp. 215-219. [DOI: https://dx.doi.org/10.1016/j.resmic.2015.01.004]

76. Pruzzo, C.; Tarsi, R.; Lleò, M.D.M.; Signoretto, C.; Zampini, M.; Colwell, R.R.; Canepari, P. In vitro adhesion to human cells by viable but nonculturable Enterococcus faecalis. Curr. Microbiol.; 2002; 45, pp. 105-110. [DOI: https://dx.doi.org/10.1007/s00284-001-0089-2] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/12070687]

77. Senoh, M.; Ghosh-Banerjee, J.; Ramamurthy, T.; Colwell, R.R.; Miyoshi, S.; Nair, G.B.; Takeda, Y. Conversion of viable but nonculturable enteric bacteria to culturable by co-culture with eukaryotic cells. Microbiol. Immunol.; 2012; 56, pp. 342-345. [DOI: https://dx.doi.org/10.1111/j.1348-0421.2012.00440.x]

78. Senoh, M.; Ghosh-Banerjee, J.; Ramamurthy, T.; Hamabata, T.; Kurakawa, T.; Takeda, M.; Colwell, R.R.; Nair, G.B.; Takeda, Y. Conversion of viable but nonculturable Vibrio cholerae to the culturable state by co-culture with eukaryotic cells. Microbiol. Immunol.; 2010; 54, pp. 502-507. [DOI: https://dx.doi.org/10.1111/j.1348-0421.2010.00245.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20840148]

79. Stern, N.; Jones, D.; Wesley, I.; Rollins, D. Colonization of chicks by non-culturable Campylobacter spp. Lett. Appl. Microbiol.; 1994; 18, pp. 333-336. [DOI: https://dx.doi.org/10.1111/j.1472-765X.1994.tb00882.x]

80. Liao, H.; Zhong, X.; Xu, L.; Ma, Q.; Wang, Y.; Cai, Y.; Guo, X. Quorum-sensing systems trigger catalase expression to reverse the oxyR deletion-mediated VBNC state in Salmonella typhimurium. Res. Microbiol.; 2019; 170, pp. 65-73. [DOI: https://dx.doi.org/10.1016/j.resmic.2018.10.004]

81. Liu, Y.; Kumblathan, T.; Uppal, G.K.; Zhou, A.; Moe, B.; Hrudey, S.E.; Li, X.F. A hidden risk: Survival and resuscitation of Escherichia coli O157:H7 in the viable but nonculturable state after boiling or microwaving. Water Res.; 2020; 183, 116102. [DOI: https://dx.doi.org/10.1016/j.watres.2020.116102] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32745672]

82. Ayrapetyan, M.; Williams, T.C.; Oliver, J.D. Interspecific quorum sensing mediates the resuscitation of viable but nonculturable vibrios. Appl. Environ. Microbiol.; 2014; 80, pp. 2478-2483. [DOI: https://dx.doi.org/10.1128/AEM.00080-14] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24509922]

83. Aktas, D.; Bagirova, M.; Allahverdiyev, A.M.; Abamor, E.S.; Safarov, T.; Kocazeybek, B.S. Resuscitation of the Helicobacter pylori coccoid forms by resuscitation promoter factor obtained from Micrococcus luteus. Curr. Microbiol.; 2020; 77, pp. 2093-2103. [DOI: https://dx.doi.org/10.1007/s00284-020-02043-x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32504323]

84. Kana, B.D.; Gordhan, B.G.; Downing, K.J.; Sung, N.; Vostroktunova, G.; Machowski, E.E.; Tsenova, L.; Young, M.; Kaprelyants, A.; Kaplan, G. et al. The resuscitation-promoting factors of Mycobacterium tuberculosisare required for virulence and resuscitation from dormancy but are collectively dispensable for growth in vitro. Mol. Microbiol.; 2008; 67, pp. 672-684. [DOI: https://dx.doi.org/10.1111/j.1365-2958.2007.06078.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18186793]

85. Lee, S.W.; Su, X.; Guo, L.; Ding, L.; Qu, K.; Shen, C. Induction of viable but nonculturable state in Rhodococcus and transcriptome analysis using RNA-seq. PLoS ONE; 2016; 11, e0147593.

86. Nikitushkin, V.D.; Demina, G.R.; Kaprelyants, A.S. Rpf proteins are the factors of reactivation of the dormant forms of actinobacteria. Biochem. Biokhimiia; 2016; 81, pp. 1719-1734. [DOI: https://dx.doi.org/10.1134/S0006297916130095]

87. Shleeva, M.; Mukamolova, G.V.; Young, M.; Williams, H.D.; Kaprelyants, A.S. Formation of ‘non-culturable’cells of Mycobacterium smegmatis in stationary phase in response to growth under suboptimal conditions and their Rpf-mediated resuscitation. Microbiology; 2004; 150, pp. 1687-1697. [DOI: https://dx.doi.org/10.1099/mic.0.26893-0]

88. Shleeva, M.O.; Kudykina, Y.K.; Vostroknutova, G.N.; Suzina, N.E.; Mulyukin, A.L.; Kaprelyants, A.S. Dormant ovoid cells of Mycobacterium tuberculosis are formed in response to gradual external acidification. Tuberculosis; 2011; 91, pp. 146-154. [DOI: https://dx.doi.org/10.1016/j.tube.2010.12.006]

89. Su, X.; Li, S.; Xie, M.; Tao, L.; Zhou, Y.; Xiao, Y.; Lin, H.; Chen, J.; Sun, F. Enhancement of polychlorinated biphenyl biodegradation by resuscitation promoting factor (Rpf) and Rpf-responsive bacterial community. Chemosphere; 2021; 263, 128283. [DOI: https://dx.doi.org/10.1016/j.chemosphere.2020.128283]

90. Su, X.; Sun, F.; Wang, Y.; Hashmi, M.Z.; Guo, L.; Ding, L.; Shen, C. Identification, characterization and molecular analysis of the viable but nonculturable Rhodococcus biphenylivorans. Sci. Rep.; 2015; 5, 18590. [DOI: https://dx.doi.org/10.1038/srep18590]

91. Su, X.; Wang, Y.; Xue, B.; Zhang, Y.; Mei, R.; Zhang, Y.; Hashmi, M.Z.; Lin, H.; Chen, J.; Sun, F. Resuscitation of functional bacterial community for enhancing biodegradation of phenol under high salinity conditions based on Rpf. Bioresour. Technol.; 2018; 261, pp. 394-402. [DOI: https://dx.doi.org/10.1016/j.biortech.2018.04.048] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29684869]

92. Su, X.; Xue, B.; Wang, Y.; Hashmi, M.Z.; Lin, H.; Chen, J.; Mei, R.; Wang, Z.; Sun, F. Bacterial community shifts evaluation in the sediments of Puyang River and its nitrogen removal capabilities exploration by resuscitation promoting factor. Ecotoxicol. Environ. Saf.; 2019; 179, pp. 188-197. [DOI: https://dx.doi.org/10.1016/j.ecoenv.2019.04.067] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31048215]

93. Ye, Z.; Li, H.; Jia, Y.; Fan, J.; Wan, J.; Guo, L.; Su, X.; Zhang, Y.; Wu, W.M.; Shen, C. Supplementing resuscitation-promoting factor (Rpf) enhanced biodegradation of polychlorinated biphenyls (PCBs) by Rhodococcus biphenylivorans strain TG9^T. Environ. Pollut.; 2020; 263, 114488. [DOI: https://dx.doi.org/10.1016/j.envpol.2020.114488] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32244156]

94. Giagnoni, L.; Arenella, M.; Galardi, E.; Nannipieri, P.; Renella, G. Bacterial culturability and the viable but non-culturable (VBNC) state studied by a proteomic approach using an artificial soil. Soil Biol. Biochem.; 2018; 118, pp. 51-58. [DOI: https://dx.doi.org/10.1016/j.soilbio.2017.12.004]

95. Pan, H.; Dong, K.; Rao, L.; Zhao, L.; Wang, Y.; Liao, X. The association of cell division regulated by DicC with the formation of viable but non-culturable Escherichia coli O157:H7. Front. Microbiol.; 2019; 10, 2850. [DOI: https://dx.doi.org/10.3389/fmicb.2019.02850] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31921032]

96. Santander, R.D.; Figas-Segura, A.; Biosca, E.G. Erwinia amylovora catalases KatA and KatG are virulence factors and delay the starvation-induced viable but nonculturable (VBNC) response. Mol. Plant Pathol.; 2017; 19, pp. 922-934. [DOI: https://dx.doi.org/10.1111/mpp.12577]

97. Mukamolova, G.V.; Kaprelyants, A.S.; Kell, D.B. Secretion of an antibacterial factor during resuscitation of dormant cells in Micrococcus luteus cultures held in an extended stationary phase. Antonie Leeuwenhoek; 1995; 67, pp. 289-295. [DOI: https://dx.doi.org/10.1007/BF00873692]

98. Mukamolova, G.V.; Kaprelyants, A.S.; Young, D.I.; Young, M.; Kell, D.B. A bacterial cytokine. Proc. Natl. Acad. Sci. USA; 1998; 95, pp. 8916-8921. [DOI: https://dx.doi.org/10.1073/pnas.95.15.8916]

99. Mukamolova, G.V.; Murzin, A.G.; Salina, E.G.; Demina, G.R.; Kell, D.B.; Kaprelyants, A.S.; Young, M. Muralytic activity of Micrococcus luteus Rpf and its relationship to physiological activity in promoting bacterial growth and resuscitation. Mol. Microbiol.; 2006; 59, pp. 84-98. [DOI: https://dx.doi.org/10.1111/j.1365-2958.2005.04930.x]

100. Su, X.; Chen, X.; Hu, J.; Shen, C.; Ding, L. Exploring the potential environmental functions of viable but non-culturable bacteria. World J. Microbiol. Biotechnol.; 2013; 29, pp. 2213-2218. [DOI: https://dx.doi.org/10.1007/s11274-013-1390-5]

101. Nikitushkin, V.D.; Demina, G.R.; Shleeva, M.O.; Guryanova, S.V.; Ruggiero, A.; Berisio, R.; Kaprelyants, A.S. A Product of RpfB and RipA joint enzymatic action promotes the resuscitation of dormant mycobacteria. FEBS J.; 2015; 282, pp. 2500-2511. [DOI: https://dx.doi.org/10.1111/febs.13292] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/25846449]

102. Martinelli, D.J.; Pavelka, M.S., Jr. The RipA and RipB Peptidoglycan Endopeptidases Are Individually Nonessential to Mycobacterium smegmatis. J. Bacteriol.; 2016; 198, pp. 1464-1475. [DOI: https://dx.doi.org/10.1128/JB.00059-16] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/26977111]

103. Hett, E.C.; Chao, M.C.; Deng, L.L.; Rubin, E.J. A mycobacterial enzyme essential for cell division synergizes with resuscitation-promoting factor. PLoS Pathog.; 2008; 4, e1000001. [DOI: https://dx.doi.org/10.1371/journal.ppat.1000001] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/18463693]

104. Hett, E.C.; Chao, M.C.; Rubin, E.J. Interaction and modulation of two antagonistic cell wall enzymes of mycobacteria. PLoS Pathog.; 2010; 6, e1001020. [DOI: https://dx.doi.org/10.1371/journal.ppat.1001020] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/20686708]

105. Signoretto, C.; Lleo, M.M.; Tafi, M.C.; Canepari, P. Cell wall chemical composition of Enterococcus faecalis in the viable but nonculturable state. Appl. Environ. Microbiol.; 2000; 66, pp. 1953-1959. [DOI: https://dx.doi.org/10.1128/AEM.66.5.1953-1959.2000]

106. Nikitushkin, V.D.; Demina, G.R.; Shleeva, M.O.; Kaprelyants, A.S. Peptidoglycan fragments stimulate resuscitation of “non-culturable” mycobacteria. Antonie Leeuwenhoek; 2013; 103, pp. 37-46. [DOI: https://dx.doi.org/10.1007/s10482-012-9784-1]

107. Panutdaporn, N.; Kawamoto, K.; Asakura, H.; Makino, S.-I. Resuscitation of the viable but non-culturable state of Salmonella enterica serovar Oranienburg by recombinant resuscitation-promoting factor derived from Salmonella Typhimurium strain LT2. Int. J. Food Microbiol.; 2006; 106, pp. 241-247. [DOI: https://dx.doi.org/10.1016/j.ijfoodmicro.2005.06.022]

108. Mir, M.; Asong, J.; Li, X.; Cardot, J.; Boons, G.J.; Husson, R.N. The extracytoplasmic domain of the Mycobacterium tuberculosis Ser/Thr kinase PknB binds specific muropeptides and is required for PknB localization. PLoS Pathog.; 2011; 7, e1002182. [DOI: https://dx.doi.org/10.1371/journal.ppat.1002182]

109. Aydin, I.; Saijo-Hamano, Y.; Namba, K.; Thomas, C.; Roujeinikova, A. Structural analysis of the essential resuscitation promoting factor YeaZ suggests a mechanism of nucleotide regulation through dimer reorganization. PLoS ONE; 2011; 6, e23245. [DOI: https://dx.doi.org/10.1371/journal.pone.0023245]

110. Handford, J.I.; Ize, B.; Buchanan, G.; Butland, G.P.; Greenblatt, J.; Emili, A.; Palmer, T. Conserved network of proteins essential for bacterial viability. J. Bacteriol.; 2009; 191, pp. 4732-4749. [DOI: https://dx.doi.org/10.1128/JB.00136-09]

111. Li, Y.; Chen, J.; Zhao, M.; Yang, Z.; Yue, L.; Zhang, X. Promoting resuscitation of viable but nonculturable cells of Vibrio harveyi by a resuscitation-promoting factor-like protein YeaZ. J. Appl. Microbiol.; 2017; 122, pp. 338-346. [DOI: https://dx.doi.org/10.1111/jam.13342] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/27966258]

112. Vecchietti, D.; Ferrara, S.; Rusmini, R.; Macchi, R.; Milani, M.; Bertoni, G. Crystal structure of YeaZ from Pseudomonas aeruginosa. Biochem. Biophys. Res. Commun.; 2016; 470, pp. 460-465. [DOI: https://dx.doi.org/10.1016/j.bbrc.2016.01.008]

113. Zhao, R.; Chen, J.; Wang, Y.; Li, Y.; Kong, X.; Han, Y. Proteolytic activity of Vibrio harveyi YeaZ is related with resuscitation on the viable but non-culturable state. Lett. Appl. Microbiol.; 2020; 71, pp. 126-133. [DOI: https://dx.doi.org/10.1111/lam.13304] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/32349168]

114. Waters, C.M.; Bassler, B.L. Quorum sensing: Cell-to-cell communication in bacteria. Annu. Rev. Cell Dev. Biol.; 2005; 21, pp. 319-346. [DOI: https://dx.doi.org/10.1146/annurev.cellbio.21.012704.131001] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/16212498]

115. Abisado, R.G.; Benomar, S.; Klaus, J.R.; Dandekar, A.A.; Chandler, J.R. Bacterial Quorum Sensing and Microbial Community Interactions. mBio; 2018; 9, e02331-e17. [DOI: https://dx.doi.org/10.1128/mBio.02331-17] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/29789364]

116. Hassett, D.J.; Ma, J.F.; Elkins, J.G.; McDermott, T.R.; Ochsner, U.A.; West, S.E.; Huang, C.T.; Fredericks, J.; Burnett, S.; Stewart, P. et al. Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. Mol. Microbiol.; 1999; 34, pp. 1082-1093. [DOI: https://dx.doi.org/10.1046/j.1365-2958.1999.01672.x] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10594832]

117. Park, K.; Kang, M.; Kim, S.H.; Lee, H.; Lim, J.; Choi, S.H.; Park, S.; Lee, K. Isolation and characterization of rpoS from a pathogenic bacterium, Vibrio vulnificus: Role of σs in survival of exponential-phase cells under oxidative stress. J. Bacteriol.; 2004; 186, pp. 3304-3312. [DOI: https://dx.doi.org/10.1128/JB.186.11.3304-3312.2004] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/15150215]

118. Li, J.; Zhao, X. Effects of quorum sensing on the biofilm formation and viable but non-culturable state. Food Res. Int.; 2020; 137, 109742. [DOI: https://dx.doi.org/10.1016/j.foodres.2020.109742]

119. McDonald, L.C.; Hackney, C.R.; Ray, B. Enhanced recovery of injured Escherichia coli by compounds that degrade hydrogen peroxide or block its formation. Appl. Environ. Microbiol.; 1983; 45, pp. 360-365. [DOI: https://dx.doi.org/10.1128/aem.45.2.360-365.1983]

120. Mizunoe, Y.; Wai, S.N.; Ishikawa, T.; Takade, A.; Yoshida, S. Resuscitation of viable but nonculturable cells of Vibrio parahaemolyticus induced at low temperature under starvation. FEMS Microbiol. Lett.; 2000; 186, pp. 115-120. [DOI: https://dx.doi.org/10.1111/j.1574-6968.2000.tb09091.x]

121. Mizunoe, Y.; Wai, S.N.; Takade, A.; Yoshida, S. Restoration of culturability of starvation-stressed and low-temperature-stressed Escherichia coli O157 cells by using H₂O₂-degrading compounds. Arch. Microbiol.; 1999; 172, pp. 63-67. [DOI: https://dx.doi.org/10.1007/s002030050741] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/10398754]

122. Vilhena, C.; Kaganovitch, E.; Grünberger, A.; Motz, M.; Forné, I.; Kohlheyer, D.; Jung, K. Importance of pyruvate sensing and transport for the resuscitation of viable but nonculturable Escherichia coli K-12. J. Bacteriol.; 2019; 201, pp. e00610-e00618. [DOI: https://dx.doi.org/10.1128/JB.00610-18] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/30420452]

123. Behr, S.; Fried, L.; Jung, K. Identification of a novel nutrient-sensing histidine kinase/response regulator network in Escherichia coli. J. Bacteriol.; 2014; 196, pp. 2023-2029. [DOI: https://dx.doi.org/10.1128/JB.01554-14] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24659770]

124. Behr, S.; Kristoficova, I.; Witting, M.; Breland, E.J.; Eberly, A.R.; Sachs, C.; Schmitt-Kopplin, P.; Hadjifrangiskou, M. Identification of a high-affinity pyruvate receptor in Escherichia coli. Sci. Rep.; 2017; 7, 1388. [DOI: https://dx.doi.org/10.1038/s41598-017-01410-2] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/28469239]

125. Kan, Y.; Lyu, Q.; Jiang, N.; Han, S.; Li, J.; Burdman, S.; Luo, L. iTRAQ-based proteomic analyses of the plant-pathogenic bacterium Acidovorax citrulli during entrance into and resuscitation from the viable but nonculturable state. J. Proteom.; 2020; 211, 103547. [DOI: https://dx.doi.org/10.1016/j.jprot.2019.103547] [PubMed: https://www.ncbi.nlm.nih.gov/pubmed/31669357]

126. Zhong, Q.; Wang, B.; Wang, J.; Liu, Y.; Fang, X.; Liao, Z. Global proteomic analysis of the resuscitation state of Vibrio parahaemolyticus compared with the normal and viable but non-culturable state. Front. Microbiol.; 2019; 10, 1045. [DOI: https://dx.doi.org/10.3389/fmicb.2019.01045]

127. Debnath, A.; Mizuno, T.; Miyoshi, S.I. Comparative proteomic analysis to characterize temperature-induced viable but non-culturable and resuscitation states in Vibrio cholerae. Microbiology; 2019; 165, pp. 737-746. [DOI: https://dx.doi.org/10.1099/mic.0.000798]

128. Lopez Marin, M.A.; Strejcek, M.; Junkova, P.; Suman, J.; Santrucek, J.; Uhlik, O. Exploring the potential of Micrococcus luteus culture supernatant with resuscitation-promoting factor for enhancing the culturability of soil bacteria. Front. Microbiol.; 2021; 12, 685263. [DOI: https://dx.doi.org/10.3389/fmicb.2021.685263]

129. Wang, Y.; Shi, J.; Tang, L.; Zhang, Y.; Zhang, Y.; Wang, X.; Zhang, X. Evaluation of Rpf protein of Micrococcus luteus for cultivation of soil actinobacteria. Syst. Appl. Microbiol.; 2021; 44, 126234. [DOI: https://dx.doi.org/10.1016/j.syapm.2021.126234]

130. Su, X.; Zhang, S.; Mei, R.; Zhang, Y.; Hashmi, M.Z.; Liu, J.; Lin, H.; Ding, L.; Sun, F. Resuscitation of viable but non-culturable bacteria to enhance the cellulose-degrading capability of bacterial community in composting. Microb. Biotechnol.; 2018; 11, pp. 527-536. [DOI: https://dx.doi.org/10.1111/1751-7915.13256]