Comparison of Fitness Cost and Virulence in Chromosome- and Plasmid-Mediated Colistin-Resistant Escherichia coli

Abstract

Five types of <i>Escherichia coli</i> strains were obtained and sequenced: colistin-susceptible (CL-S) strains, <i>in vitro</i> induced colistin-resistant (CL-IR) strains, <i>mcr-1-</i>negative colistin-resistant strains from livestock (CL-chrR), <i>mcr-1</i>-positive colistin-resistant strains (CL-mcrR), and <i>mcr-1</i>-transferred transconjugants (TC-mcr). Amino acid alterations of PmrAB, PhoPQ, and EptA were identified, and their mRNA expression was measured. Their growth rate was evaluated, and an <i>in vitro</i> competition assay was performed. Virulence was compared through serum resistance and survival in macrophages and <i>Drosophila melanogaster</i>. CL-IR and CL-chrR strains were colistin-resistant due to amino acid alterations in PmrAB, PhoPQ, or EptA, and their overexpression. All colistin-resistant strains did not show reduced growth rates compared with CL-S strains. CL-IR and CL-chrR strains were less competitive than the susceptible strain, but CL-mcrR strains were not. In addition, TC-mcr strains were also significantly more competitive than their respective parental susceptible strain. CL-IR strains had similar or decreased survival rates in human serum, macrophages, and fruit flies, compared with their parental, susceptible strains. CL-chrR strains were also less virulent than CL-S strains. Although CL-mcrR strains showed similar survival rates in human serum and fruit fly to CL-S strains, the survival rates of TC-mcr strains decreased significantly in human serum, macrophages, and fruit flies, compared with their susceptible recipient strain (J53). Chromosome-mediated, colistin-resistant <i>E. coli</i> strains have a fitness cost, but plasmids bearing <i>mcr-1</i> do not increase the fitness burden of <i>E. coli</i>. Along with high usage of polymyxins, the no fitness cost of <i>mcr-1</i>-positive strains may facilitate rapid spread of colistin resistance.