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Figure 1. Candida albicans biofilm resistance mechansisms. Resistance mechanisms at the (A) community and (B) cellular level.
(Figure omitted. See article PDF.)
Antimicrobial drug resistance is an obstacle to the treatment of numerous infectious diseases [1,2]. One the most commonly recognized types of drug resistance is the ability of microorganisms to produce resilient biofilms on the surface of implanted medical devices [1-3]. When adopting this lifestyle, Candida proliferates as a community of adherent cells encased in an extracellular matrix. These biofilms display innate resistance to multiple drug classes and are capable of withstanding antifungal concentrations 1000-fold higher than those that inhibit nonbiofilm, planktonic cells [4-7]. Since common drug therapies do not eradicate Candida biofilms, removal of the infected device is almost always necessary to cure the infection [8-11]. Treatment is difficult as the medical devices are often critical for patient care and currently available antifungal therapies are virtually ineffective [7,9,12,13]. Candida biofilm infections, if not successfully treated, can have devastating consequences, progressing to bloodstream infections and invasive fungal infections with high risks of mortality. Many of the pioneering biofilm investigations, and this review, focus on Candida albicans [14-16]. However, it is becoming increasingly clear that numerous Candida spp., including Candida glabrata , Candida parapsilosis, Candida dubliniensis and Candida tropicalis , also cause recalcitrant device-associated infections.
Striking antifungal resistance is an intrinsic biofilm characteristic, and one of the many phenotypic changes that occurs upon transition to this mode of growth [8,17]. Although the resistant phenotype is most pronounced during the later phases of development, drug resistance can be detected within minutes to hours of surface adherence [8]. This resistance does not involve acquisition of genetic mutations, since biofilm cells recultured in planktonic conditions are susceptible to antifungals. Candida biofilm resistance to antifungal therapy appears to be multifactorial, with diverse mechanisms working in a coordinated fashion throughout the various stages of biofilm growth [18-20]. Here we will review the multiple mechanisms that contribute to the extraordinary drug resistance of Candida (mostly C. albicans ) biofilms. We first include a brief overview of four drug classes commonly used to treat Candida infections: the azoles, the polyenes (amphotericin B), the echinocandins and 5-flucytosine.
Overview of antifungal classes with activity against Candida spp
Azoles
Triazole antifungal drugs inhibit growth of