ABSTRACT
OBJECTIVES: Butyrate is a short-chain fatty acid that is produced by several human commensal bacteria, such as Clostridium and Lactobacillus species. Butyrate is also known to inhibit histone deacetylase. In this study we assessed the antifungal activity of sodium butyrate (SB) against the human pathogenic yeasts Candida albicans, Candida parapsilosis and Cryptococcus neoformans. METHODS: The growth and virulence traits of the yeasts were assayed in vitro and during interaction with macrophages in the presence of SB. RESULTS: SB strongly inhibited yeast growth in a concentration-dependent manner, inhibited virulence traits such as filamentation in C. albicans and melanization and capsule formation in C. neoformans and, importantly, significantly decreased yeast biofilm formation. SB also enhanced the antifungal activity of azole drugs. Notably, SB augmented the antifungal activity of macrophages by enhancing the production of reactive oxygen species. The phagocytic rate and killing activity of macrophages significantly increased in the presence of SB, which coincided with an increase in nitric oxide production. CONCLUSIONS: These results demonstrate that SB exerts significant antifungal activity on pathogenic yeasts and enhances the antimicrobial actions of macrophages in response to these microbes.
Subject(s)
Antifungal Agents/pharmacology , Butyrates/pharmacology , Candida albicans/drug effects , Cryptococcus neoformans/drug effects , Macrophages/metabolism , Azoles/pharmacology , Biofilms/drug effects , Candida albicans/growth & development , Candida albicans/pathogenicity , Clostridium/metabolism , Cryptococcus neoformans/growth & development , Cryptococcus neoformans/pathogenicity , Histone Deacetylase Inhibitors/pharmacology , Lactobacillus/metabolism , Macrophages/immunology , Macrophages/microbiology , Microbial Sensitivity Tests , Nitric Oxide/biosynthesis , Phagocytosis/drug effects , Phenotype , Reactive Oxygen Species/metabolismABSTRACT
Monoclonal antibodies to Histoplasma capsulatum can modify pathogenesis. We now show that monoclonal antibody H1C to a 70-kDa antigen increases intracellular fungal growth and reduces macrophage nitric oxide release but has no effect on fungal burden or survival in murine infection. This further demonstrates the complexities of host-pathogen interactions.
