532 Three-dimensional structure of a microbial nanomachine and its role in acne vulgaris

Treating acne with antibiotics has led to the emergence of multidrug resistant (MDR) bacteria. MDR bacterial infections incur high healthcare costs and result in higher patient mortality. New that target specific bacteria avoid collateral microbiota damage are needed. Antibiotics used treat reduce levels Cutibacterium acnes. Acne-associated C. acnes genomes include putative, non-ribosomal peptide synthetase (NRPS) genes. Microbes use NRPS proteins assemble unique metabolites. Some these metabolites virulence factors (e.g., Escherichia coli siderophores). Inhibiting been proposed as a strategy minimize antibiotic damage. No yet characterized. One acne-associated genes (PPA-RS12630) is found almost exclusively within Propionibacterium genus, which includes Based on sequence homology, we hypothesize PPA-RS12630 an iterative tri-domain structure consisting adenylation, peptidyl carrier, condensation domains. synthesize siderophore vicibactin using this type NRPS. Our group prediction programs design E. expression construct. Recombinant was expressed, purified, biochemical structural investigations. Negative-stain electron microscopy recombinant demonstrated flexible, consistent Cryogenic (cryoEM) data collected determine its three-dimensional structure. The high-resolution protein will provide road map guide characterization other related proteins. These investigations help us understand role human diseases, develop precision therapeutics, decrease burden infections.