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Rapid and consistent evolution of colistin resistance in Pseudomonas aeruginosa during morbidostat culture

By Bianca Regenbogen, Matthias Willmann, Matthias Steglich, Boyke Bunk, Ulrich Nubel, Silke Peter, Richard A Neher

Posted 14 Oct 2016
bioRxiv DOI: 10.1101/080960 (published DOI: 10.1128/AAC.00043-17)

Colistin is a last resort antibiotic commonly used against multidrug-resistant strains of Pseudomonas aeruginosa. To investigate the potential for in-situ evolution of resistance against colistin and map the molecular targets of colistin resistance, we exposed two P. aeruginosa isolates to colistin using a continuous culture device known as morbidostat. Colistin resistance emerged within two weeks along with highly stereotypic yet strain specific mutation patterns. The majority of mutations hit the prmAB two component signaling system and genes involved in lipopolysaccharide synthesis, including lpxC, pmrE, and migA. In seven out of 18 cultures, we observed mutations in mutS along with a mutator phenotype that seemed to facilitate resistance evolution.

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