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

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...

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Bibliographic Details
Published inbioRxiv
Main Authors Regenbogen, Bianca, Willmann, Matthias, Steglich, Matthias, Bunk, Boyke, Ulrich N bel, Silke, Peter, Neher, Richard A
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 14.10.2016
Subjects
Colistin
Continuous culture
Evolution
Lipopolysaccharides
Multidrug resistance
Mutation
Phenotypes
Pseudomonas aeruginosa
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Summary: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.
DOI:10.1101/080960