%0 Journal Article %A Axel B. Janssen %A Toby L. Bartholomew %A Natalia P. Marciszewska %A Marc J.M. Bonten %A Rob J.L. Willems %A Jose A. Bengoechea %A Willem van Schaik %T Mechanisms of colistin resistance in Escherichia strains isolated from bloodstream infections %D 2019 %R 10.1101/864983 %J bioRxiv %P 864983 %X 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. %U https://www.biorxiv.org/content/biorxiv/early/2019/12/05/864983.full.pdf