@article {Janssen864983, author = {Axel B. Janssen and Toby L. Bartholomew and Natalia P. Marciszewska and Marc J.M. Bonten and Rob J.L. Willems and Jose A. Bengoechea and Willem van Schaik}, title = {Mechanisms of colistin resistance in Escherichia strains isolated from bloodstream infections}, elocation-id = {864983}, year = {2019}, doi = {10.1101/864983}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Infections by multidrug-resistant Gram-negative bacteria are increasingly common, prompting the renewed interest in the use of colistin. Colistin specifically targets Gram-negative bacteria by interacting with the anionic lipid A moieties of lipopolysaccharides, leading to membrane destabilization and cell death. Here, we aimed to uncover colistin resistance mechanisms in ten colistin-resistant Escherichia strains out of 1140 bloodstream isolates, originating from patients hospitalised in a tertiary hospital over a ten-year period (2006 - 2015). Core genome phylogenetic analysis showed that each patient was colonised by a unique strain, suggesting that colistin-resistant strains were acquired independently in each case. All colistin-resistant strains had lipid A that was modified with phosphoethanolamine. One strain carried the mobile colistin resistance gene mcr-1.1. Through construction of chromosomal transgene integration mutants, we experimentally determined that mutations in basRS, encoding a two-component signal transduction system, led to colistin resistance in four strains. While colistin resistance in E. coli can be acquired through mcr-1.1, sequence variation in basRS is another, potentially more prevalent but underexplored, cause of colistin resistance.}, URL = {https://www.biorxiv.org/content/early/2019/12/05/864983}, eprint = {https://www.biorxiv.org/content/early/2019/12/05/864983.full.pdf}, journal = {bioRxiv} }