Mechanisms of colistin resistance in Escherichia strains isolated from bloodstream infections

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.