Abstract
ABSTRACTBacteria interact with each other in nature and often compete for limited nutrient and space resources. However, it is largely unknown whether and how bacteria also interact with human fungal pathogens naturally found in the environment. Here, we identified a soil bacterium, Bacillus safensis, which potently blocked several key Cryptococcus neoformans virulence factors, including formation of the antioxidant pigment melanin and production of the antiphagocytic polysaccharide capsule. The bacterium also inhibited de novo cryptococcal biofilm formation but had only modest inhibitory effects on already formed biofilms or planktonic cell growth. The inhibition of fungal melanization was dependent on direct cell contact and live bacteria. B. safensis also had anti-virulence factor activity against another major human-associated fungal pathogen, Candida albicans. Specifically, dual-species interaction studies revealed that the bacterium strongly inhibited C. albicans filamentation and biofilm formation. In particular, B. safensis physically attached to and degraded candidal filaments. Through genetic and phenotypic analyses, we demonstrated that bacterial chitinase activity against fungal cell wall chitin is a factor contributing to the antipathogen effect of B. safensis.
Highlights
Bacteria interact with each other in nature and often compete for limited nutrient and space resources
The soil samples were previously shown to be positive for the presence of C. gattii, and we hypothesized that this would increase our chances of identifying microbes with anticryptococcal activity [15]
The ert1Δ mutant, behaved like the wild type in this assay, and sorbitol did rescue melanin formation in the presence of B. safensis. These results indicated that the cell wall integrity (CWI) pathway may be involved in resistance to B. safensis-mediated fungal targeting
Summary
Bacteria interact with each other in nature and often compete for limited nutrient and space resources. Human fungal pathogens are responsible for over two million deaths annually [1, 2] To establish infections, these fungi rely on a set of specific virulence factors such as, for example, the production of a protective polysaccharide capsule, pigment biosynthesis, secretion of enzymes, biofilm formation, and morphological plasticity. A novel concept in antimicrobial development has emerged to develop therapies that exclusively target microbial virulence factor elaboration instead of eradication of the pathogen itself [6]. This approach can be seen as disarming pathogenic microorganisms and rendering them harmless and/or more susceptible to containment by antibiotics or the human immune system. Cryptococcal infections are responsible for 15% of all AIDS-related deaths worldwide [8]
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