A Potential Antifungal Effect of Chitosan Against Is Mediated via the Inhibition of SAGA Complex Component Expression and the Subsequent Alteration of Cell Surface Integrity.

Due to the high incidence of nosocomial infection, the first-line drugs for infection have been heavily used, and the emergence of drug-resistant strains has gradually increased. Thus, a new antifungal drug or therapeutic method is needed. Chitosan, a product of chitin deacetylation, is considered to be potentially therapeutic for fungal infections because of its excellent biocompatibility, biodegradability and low toxicity. The biocidal action of chitosan against shows great commercial potential, but the exact mechanisms underlying its antimicrobial activity are unclear. To reveal these mechanisms, mutant library screening was performed. gene, which encodes a histone acetylation coactivator in the SAGA complex, was identified. Transmission electronic microscopy images showed that the surface of chitosan-treated Δ cells was substantially disrupted and displayed an irregular morphology. Interestingly, the cell wall of Δ cells was significantly thinner than that of wild-type cells, with a thickness similar to that seen in the chitosan-treated wild-type strain. Although is required for chitosan tolerance, expression of and several Ada2-mediated cell wall-related genes (, and ) and efflux transporter genes ( and ) were significantly inhibited by chitosan. Furthermore, encoding a SAGA complex catalytic subunit was inhibited by chitosan, and Δ cells exhibited phenotypes comparable to those of Δ cells in response to chitosan and other cell surface-disrupting agents. This study demonstrated that a potential antifungal mechanism of chitosan against operates by inhibiting SAGA complex gene expression, which decreases the protection of the cell surface against chitosan.