Rapid evolution drives the rise and fall of carbapenem resistance during an acute Pseudomonas aeruginosa infection

摘要: Abstract It is well established that antibiotic treatment selects for resistance in pathogenic bacteria. However, the evolutionary responses of pathogen populations to during infections remain poorly resolved, especially acute infections. Here we map high definition through genomic and phenotypic characterization >100 isolates from a patient with P. aeruginosa pneumonia. Antibiotic therapy (meropenem, colistin) caused rapid crash population lung, but this decline was followed by spread meropenem mutations restrict uptake (oprD) or modify LPS biosynthesis (wbpM). Low fitness strains high-level were then replaced ‘anti-resistance’ MexAB-OprM efflux pump, causing both collateral loss broad spectrum antibiotics. In contrast, did not observe any intestinal aeruginosa. Carbapenem antibiotics are key Gram negative pathogens, our work highlights ability natural selection drive rise fall carbapenem