Importance of Candida-bacterial polymicrobial biofilms in disease

Abstract

Candida albicans is the most prevalent human fungal pathogen, with an ability to inhabit diverse host niches and cause disease in both immunocompetent and immunocompromised individuals. C. albicans also readily forms biofilms on indwelling medical devices and mucosal tissues, which serve as an infectious reservoir that is difficult to eradicate, and can lead to lethal systemic infections. Biofilm formation occurs within a complex milieu of host factors and other members of the human microbiota. Polymicrobial interactions will probably dictate the cellular and biochemical composition of the biofilm, as well as influence clinically relevant outcomes, such as drug and host resistance and virulence. In this manuscript, we review C. albicans infections in the context of in vivo polymicrobial biofilms and implications for pathogenesis.

Figure 1

Polymicrobial biofilm of C. albicans and S. aureus. C. albicans SC5314 was grown overnight in Sabouraud dextrose broth (SDB) at 30°C. S. aureus 29523 was grown overnight at 37°C in brain heart infusion (BHI) broth. Both species were washed, counted, and diluted in RPMI-1640 medium + 10% FBS. C. albicans (10⁶ CFU/ml) and S. aureus to (10⁷ CFU/ml) were concurrently added to 96-well tissue culture-treated chamber slides and incubated for 24 h at 37°C. Biofilm formation was monitored by fluorescence microscopy and scanning electron microscopy. To visualize the fungi and bacteria, biofilms were stained with SYTO 9 (green, live bacteria), FUN-1 (intracellular red, live fungal cells), calcofluor white (blue, fungal cell wall). Magnification of 1000×. Abbreviations: Ca, C. albicans hyphae; Sa, S. aureus.

Figure 2

Polymicrobial biofilms formed on dentures from a rat model of C. albicans denture stomatitis. A denture system was installed in Wistar rats that consists of a custom-fitted removable plate that fits over the rat palate and a fixed denture that is anchored to the rear molars. C. albicans 3153A was grown overnight in SDB at 30°C. Rats were inoculated with 25 mg of pelleted yeast on the palate tissue underlying the removable denture. Dentures were removed at 6 weeks post-inoculation and biofilm formation was analyzed by scanning electron microscopy. (a) 1000×, (b) 4000× magnification. Scale bar indicates 50 μM. Abbreviations: Ca, C. albicans hyphae; B, bacteria.