Biochemometric Analysis of Bat Skin Microbiome-Associated <i>Streptomyces buecherae</i> Identifies Polyether Antibiotics Active Against the Bat Pathogen <i>Pseudogymnoascus destructans</i>

Background Bats, critical to controlling insect populations, harbor unique immune systems that can provide insight into preventing and treating diseases. Unfortunately, white-nose syndrome (WNS), caused by the fungus Pseudogymnoascus destructans, has devastated North American bat populations, killing millions since the winter of 2006 in one of the greatest wildlife disease epidemics in U.S. history. Several reports have found evidence that bat microbiomes play a role in protecting their host against WNS. However, investigations into the antifungal metabolites produced by these symbionts are extremely limited. Objective The aim of this study was to investigate the antifungal constituents of Streptomyces buecherae, a novel bat-associated bacterium isolated from bats in New Mexico. Methods To identify bioactive compounds from the complex bacterial extract, we combined untargeted mass spectrometry metabolomics with in vitro antifungal activity data against P. destructans , identifying a suite of antifungal metabolites for targeted study using biochemometric partial least squares analyses combined with molecular networking. Results The metabolomics analyses revealed that nigericin—a known polyether antibiotic—was the major bioactive compound in the extract, and molecular networking revealed additional nigericin analogs present in the bioactive extract. Nigericin showed moderate antifungal activity against P. destructans in a disc diffusion assay down to a concentration of 6.25 μg/disc. Conclusions Nigericin is the primary bioactive constituent present in S. buecherae extracts that may be responsible for the antifungal effect this bacterium shows against P. destructans in vitro. This study underscores the potential of bat-associated Streptomyces species in combatting fungal pathogens and provides insight into the chemical mechanisms involved in bat microbiome defenses against WNS.