Colistin is a last-resort antibiotic commonly used against multidrug-resistant strains of To investigate the potential for evolution of resistance against colistin and to map the molecular targets of colistin resistance, we exposed two isolates to colistin using a continuous-culture device known as a morbidostat. As a result, colistin resistance reproducibly increased 10-fold within 10 days and 100-fold within 20 days, along with highly stereotypic yet strain-specific mutation patterns. The majority of mutations hit the two-component signaling system and genes involved in lipopolysaccharide (LPS) synthesis, including , , and We tracked the frequencies of all arising mutations by whole-genome deep sequencing every 3 to 4 days to obtain a detailed picture of the dynamics of resistance evolution, including competition and displacement among multiple resistant subpopulations. In 7 out of 18 cultures, we observed mutations in along with a mutator phenotype that seemed to facilitate resistance evolution.
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| http://dx.doi.org/10.1128/AAC.00043-17 | DOI Listing |
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