Pearls Fungal Biofilms

Biofilms are a principal form of microbial growth and are critical to development of clinical infection. They are responsible for a broad spectrum of microbial infections in the human host. Many medically important fungi produce biofilms, including Candida [1], Aspergillus [2], Cryptococcus [3], Trichosporon [4], Coccidioides [5], and Pneumocystis [6]. In this review we emphasize common features among fungal biofilms, and point toward genes and pathways that may have conserved roles. Biofilm cell communities are more resistant to antifungal drugs than planktonic cells. Contributing factors include biofilm structural complexity, presence of extracellular matrix (ECM), metabolic heterogeneity intrinsic to biofilms, and biofilm-associated up-regulation of efflux pump genes. The actual fold increase in resistance varies with both the drug and species. Candida albicans and Candida parapsilosis biofilms are relatively resistant to fluconazole, amphotericin B, nystatin, voriconazole, and others. Aspergillus fumigatus biofilms are relatively resistant to itraconazole and, to some extent, to caspofungin. Cryptococcal biofilms are unaffected by fluconazole and voriconazole, and biofilms of Trichosporon asahii display elevated resistance to amphotericin B, caspofungin, voriconazole, and fluconazole. Azole and amphotericin B therapies are ineffective against Pneumocystis carinii biofilms. Biofilm-associated resistance mechanisms have been characterized in C. albicans and A. fumigatus and include drug binding by ECM and production of persister cells [2,7] (see supplementary references for this section in Text S1). Persister cells represent only a fraction of the population, and probably reflect its metabolic heterogeneity. These mechanisms may pertain to other fungi as well.