Project description:MRSA genomic epidemiology in Saudi Arabia
| PRJEB59751 | ENA
Project description:A comprehensive study of the population dynamics of Hospital-Acquired MRSA using genomic epidemiology within a healthcare facility in Saudi Arabia.
Project description:A comprehensive study of the population dynamics of Hospital-Acquired MRSA using genomic epidemiology within a healthcare facility in Saudi Arabia
Project description:In this study, we report the genome-wide expression profiles of hospital-acquired and community-acquired P. aeruignosa. The analysis of that provides crucial implications concerning the virulence determinants associated with the community-acquired diarrheagenic strain of P. aeruginosa
Project description:Pseudomonas aeruginosa is a leading cause of hospital acquired infections for which the development of new antibiotics is urgently needed. Unlike most enteric bacteria, P. aeruginosa lacks thymidine kinase and thymidine phosphorylase activity, and thus cannot scavenge exogenous thymine. An appealing strategy to selectively target P. aeruginosa while leaving the healthy microbiome largely intact would thus be to disrupt thymidine synthesis while providing exogenous thymine. However, this approach was previously intractable because known antibiotics that perturb thymidine synthesis are largely inactive against P. aeruginosa. Here, we characterize a novel dihydrofolate reductase inhibitor, fluorofolin, that exhibits significant activity against P. aeruginosa in culture and in a mouse thigh infection model. Fluorofolin is active against a wide range of clinical P. aeruginosa isolates resistant to known antibiotics, including critical antibiotic development priorities expressing the beta-lactamases KPC-5 and NDM-1. Importantly, in the presence of thymine supplementation, fluorofolin activity is selective for P. aeruginosa. Resistance to fluorofolin can emerge through overexpression of the efflux pumps MexCD-OprJ and MexEF-OprN. However, these mutants also decrease pathogenesis, in part due to increased export of quorum sensing precursors leading to decreased virulence factor production. Our findings thus demonstrate how understanding species-specific genetic differences and discovery of an antibiotic with a widely conserved target can enable selective targeting of important pathogens while revealing new tradeoffs between resistance and pathogenesis.
Project description:Pseudomonas aeruginosa is a common bacterium in the terminal plumbing system of buildings and it is from this niche that a substantial fraction of infections are acquired. To better understand P. aeruginosa biology in this environment, we examined the transcriptomes in tap water and pond water.
