Identification of drug-resistance determinants in a clinical isolate of Pseudomonas aeruginosa by high-density transposon mutagenesis.

Identification of drug-resistance determinants in a clinical isolate of Pseudomonas aeruginosa by high-density transposon mutagenesis. Antimicrob Agents Chemother. 2019 Dec 09;: Authors: Sonnabend MS, Klein K, Beier S, Angelov A, Kluj R, Mayer C, Groß C, Hofmeister K, Beuttner A, Willmann M, Peter S, Oberhettinger P, Schmidt A, Autenrieth IB, Schütz M, Bohn E Abstract With the aim to identify potential new targets to restore antimicrobial susceptibility of multidrug-resistant (MDR) Pseudomonas aeruginosa (Pa), we generated a high-density transposon (Tn) insertion mutant library in a MDR Pa bloodstream isolate (ID40). The depletion of Tn insertion mutants upon exposure to cefepime or meropenem was measured in order to determine the common resistome for these clinically important antipseudomonal β-lactam antibiotics. The approach was validated by clean deletions of genes involved in peptidoglycan synthesis/recycling such as the lytic transglycosylase MltG, the murein endopeptidase MepM1, the MurNAc/GlcNAc-kinase AmgK and the uncharacterized protein YgfB that all were identified in our screen as playing a decisive role for survival of treatment with cefepime or meropenem. We found that the antibiotic resistance of Pa can be overcome by targeting usually non-essential genes that turn essential in the presence of therapeutic concentrations of antibiotics. For all validated genes, we demonstrated that their deletion leads to the reducti...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research