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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background: Colistin resistance among Gram-negative nosocomial pathogens is an increasing concern. The bacteriophage-encoded lytic enzyme endolysin LysAB1245, which targets bacterial peptidoglycan, was evaluated as a potential antibacterial agent in combination with colistin as a therapeutic approach. Methods: Clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, along with two reference strains, were used to assess the antibacterial activity of LysAB1245 and colistin, individually and in combination. Antibacterial susceptibility was assessed by broth microdilution. Synergistic interactions were determined using checkerboard assays and confirmed by time-kill kinetics. Resistance development was assessed after several rounds of exposure to each agent, either alone or in combination. Results: In this study, the synergistic activity of the LysAB1245/colistin combination therapy was found in some clinical isolates of Acinetobacter baumannii and Pseudomonas aeruginosa, resulting in a reduction in the MICs of both LysAB1245 and colistin. The bactericidal effects, with a significant, more than 3-log reduction in CFU/mL (p < 0.01), were observed in representative synergistic isolates within 4 h of treatment with the combination of LysAB1245 at 1/4 × MIC and colistin at 1/4 × MIC. Scanning electron microscope micrographs confirmed bacterial cell damage upon treatment with the combination. Additionally, treatment with LysAB1245 in combination with colistin had no effect on the development of bacterial resistance after multiple passages. Conclusions: Combining LysAB1245 with a last-resort antibiotic like polymyxins (colistin) could be used as a promising new antibacterial strategy for preventing and controlling antibiotic-resistant Gram-negative bacteria.

Details

Title
Efficacy of Endolysin LysAB1245 Combined with Colistin as Adjunctive Therapy Against Colistin-Resistant Gram-Negative Bacteria
Author
Rosesathorn, Soontarach 1   VIAFID ORCID Logo  ; Piyawan, Voravuthikunchai Supayang 2   VIAFID ORCID Logo  ; Srimanote Potjanee 3 ; Sarunyou, Chusri 4   VIAFID ORCID Logo 

 Center of Antimicrobial Biomaterial Innovation-Southeast Asia, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand; [email protected] (R.S.); [email protected] (S.P.V.), Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand, Department of Medical Technology, School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80161, Thailand 
 Center of Antimicrobial Biomaterial Innovation-Southeast Asia, Faculty of Science, Prince of Songkla University, Songkhla 90110, Thailand; [email protected] (R.S.); [email protected] (S.P.V.) 
 Graduate in Biomedical Sciences, Faculty of Allied Health Sciences, Thammasat University, Pathum Thani 12121, Thailand; [email protected] 
 Division of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand 
First page
538
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
20796382
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3223866280
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.