RT Journal Article SR Electronic T1 Rapid and consistent evolution of colistin resistance in Pseudomonas aeruginosa during morbidostat culture JF bioRxiv FD Cold Spring Harbor Laboratory SP 080960 DO 10.1101/080960 A1 Bianca Regenbogen A1 Matthias Willmann A1 Matthias Steglich A1 Boyke Bunk A1 Ulrich NĂ¼bel A1 Silke Peter A1 Richard A. Neher YR 2016 UL http://biorxiv.org/content/early/2016/10/14/080960.abstract AB 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.