Scientists studied two enzymes from a yeast that can break down important human antimicrobial proteins like LL‑37. These enzymes work in slightly acidic to neutral conditions, aren’t stopped by a common inhibitor, and can affect fungal biofilms and immune responses in an insect model. The work mainly explains how this yeast might evade our defenses, but it doesn’t give direct tips for health‑hacking or longevity.

Candida glabrata (currently classified as Nakaseomyces glabratus) is an opportunistic yeast-like fungus that causes infections in humans, with limited treatment options due to resistance to antifungal drugs. In contrast to C. albicans, which produces secreted aspartic proteases (Saps) involved in pathogenicity, C. glabrata expresses a distinct group of cell surface-associated aspartic proteases known as yapsins (Yps). While YPS gene deletion mutants have proposed roles in cellular homeostasis, their precise contribution to fungal virulence and host interactions remains unclear. Herein, we present the first detailed biochemical and functional characterization of two native Yps proteins, Yps3 and Yps9, purified from C. glabrata cultures. Both proteases displayed robust activity in a mildly acidic to neutral pH range (5.5-7.0), resistance to the classical aspartic protease inhibitor pepstatin A, and selectively degraded key host antimicrobial peptides, including LL-37 cathelicidin, histatin 5 (Hst5), and kininogen-derived peptide NAT26, by hydrolyzing lysine residues. Additionally, Yps9 promoted C. albicans biofilm dispersal. In a Galleria mellonella infection model, a pre-treatment with each protease enhanced larval survival and increased phenol oxidase activity, implying a role of yapsins in immune priming. Collectively, these findings reveal multifunctional roles for Yps3 and Yps9 in fungal virulence, biofilm modulation, and host immune interactions.