PT - JOURNAL ARTICLE AU - Axel B. Janssen AU - Toby L. Bartholomew AU - Natalia P. Marciszewska AU - Marc J.M. Bonten AU - Rob J.L. Willems AU - Jose A. Bengoechea AU - Willem van Schaik TI - Mechanisms of colistin resistance in <em>Escherichia</em> strains isolated from bloodstream infections AID - 10.1101/864983 DP - 2019 Jan 01 TA - bioRxiv PG - 864983 4099 - http://biorxiv.org/content/early/2019/12/05/864983.short 4100 - http://biorxiv.org/content/early/2019/12/05/864983.full AB - 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.