ena-STUDY-CENTRO SUPERIOR DE INVESTIGACION EN SALUD PUBLICA-16-10-2020-13:17:32:585-378
Metatranscriptomic analysis of fecal microbiota from mice to identify the mechanism by which ProBac inhibits VRE colonization
Multidrug resistant pathogens (MRP), including vancomycin-resistant Enterococcus (VRE), have become a major threat to public health. Some MRP strains can be resistant to all antibiotics available, thus alternative strategies to antibiotics are urgently needed to combat these challenging pathogens. MRP infections, including those produced by VRE, frequently start by colonization of the intestinal tract, a crucial step that is impaired by the presence of the intestinal microbiota. Despite its relevance, the members of the microbiota that suppress MRP gut colonization and the mechanisms of such protection are largely unknown.In the present study, we combined 16s rDNA sequencing of the gut microbiota to identify commensal bacteria associated with protection against VRE colonization. We next assembled a consortium containing five of the putative protective commensals and showed that administration of these bacteria was sufficient to restrict VRE gut colonization in antibiotic treated mice. Finally, we combined sequencing of the putative probiotic genomes with metatranscriptomics, targeted metabolomics and in vivo assays to identify the mechanism by which the bacterial consortium inhibits VRE growth.
Multidrug resistant pathogens (MRP), including vancomycin-resistant Enterococcus (VRE), have become a major threat to public health. Some MRP strains can be resistant to all antibiotics available, thus alternative strategies to antibiotics are urgently needed to combat these challenging pathogens. MRP infections, including those produced by VRE, frequently start by colonization of the intestinal tract, a crucial step that is impaired by the presence of the intestinal microbiota. Despite its relevance, the members of the microbiota that suppress MRP gut colonization and the mechanisms of such protection are largely unknown.In the present study, we combined 16s rDNA sequencing of the gut microbiota to identify commensal bacteria associated with protection against VRE colonization. We next assembled a consortium containing five of the putative protective commensals and showed that administration of these bacteria was sufficient to restrict VRE gut colonization in antibiotic treated mice. Finally, we combined sequencing of the putative probiotic genomes with metatranscriptomics, targeted metabolomics and in vivo assays to identify the mechanism by which the bacterial consortium inhibits VRE growth.