Sophie S. Son

Rapid bacterial identification remains a critical challenge in infectious disease diagnostics. We developed a novel molecular approach to detect and identify a wide diversity of bacterial pathogens in a single, simple assay, exploiting the conservation, abundance, and rich phylogenetic content of ribosomal RNA in a rapid fluorescent hybridization assay that requires no amplification or enzymology. Of 117 isolates from 64 species across 4 phyla, this assay identified bacteria with >89% accuracy at the species level and 100% accuracy at the family level, enabling all critical clinical distinctions. In pilot studies on primary clinical specimens, including sputum, blood cultures, and pus, bacteria from 5 different phyla were identified.

Abstract A subset of commensal bacterial strains secrete bacteriocins, such as lantibiotics, to establish and protect their niche in the gut. Because the antimicrobial spectrum of lantibiotics includes opportunistic pathogens, such as vancomycin-resistant Enterococcus faecium (VRE), they may provide an approach to reduce antibiotic-resistant infections. The impact of lantibiotic-producing bacteria on the complex microbial populations constituting the microbiome, however, remains poorly defined. We find that genes encoding lanthipeptides, including lantibiotics, are commonly present in the microbiomes of healthy humans and in dysbiotic microbiomes of hospitalized patients. In fecal samples collected from hospitalized patients, bacterial species encoding lantibiotic genes are present in greater abundance than lantibiotic-deficient strains of the same species. We demonstrate that the lantibiotic-producing bacterium, Blautia pseudococcoides SCSK, prevents intestinal recolonization of mice by a wide range of commensal species following antibiotic-induced dysbiosis and markedly reduces fecal concentrations of microbiota-derived metabolites associated with mucosal immune defenses. Lantibiotic-mediated dysbiosis results in sustained loss of colonization resistance against Klebsiella pneumoniae and Clostrioides difficile infection. Our findings reveal the potential impact of lantibiotic-producing bacterial species on microbiome resilience and susceptibility to infection following antibiotic treatment.