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• W2809749880 abstract "Abstract Colistin remains one of the few antibiotics effective against multi-drug resistant (MDR) hospital pathogens, such as Klebsiella pneumoniae . Yet resistance to this last-line drug is rapidly increasing. Characterized mechanisms of col R in K . pneumoniae are largely due to chromosomal mutations in two-component regulators, although a plasmid-mediated col R mechanism has recently been uncovered. However, the effects of intrinsic colistin resistance are yet to be characterized on a whole-genome level. Here, we used a genomics-based approach to understand the mechanisms of adaptive col R acquisition in K . pneumoniae . In controlled directed-evolution experiments we observed two distinct paths to colistin resistance acquisition. Whole genome sequencing identified mutations in two colistin resistance genes: in the known col R regulator phoQ which became fixed in the population and resulted in a single amino acid change, and unstable minority variants in the recently described two-component sensor crrB . Through RNAseq and microscopy, we reveal the broad range of effects that colistin exposure has on the cell. This study is the first to use genomics to identify a population of minority variants with mutations in a col R gene in K . pneumoniae ." @default.
• W2809749880 created "2018-07-10" @default.
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• W2809749880 date "2018-06-29" @default.
• W2809749880 modified "2023-09-26" @default.
• W2809749880 title "Morphological, genomic and transcriptomic responses of Klebsiella pneumoniae to the last-line antibiotic colistin" @default.
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• W2809749880 doi "https://doi.org/10.1038/s41598-018-28199-y" @default.
• W2809749880 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6026146" @default.
• W2809749880 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29959380" @default.
• W2809749880 hasPublicationYear "2018" @default.
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