Impact of the colistin resistance gene mcr-1 on bacterial fitness

A Klebsiella pneumoniae isolate harbouring a 217 kb IncHI2-type plasmid (pKP2442) encoding the colistin resistance gene mcr-1 was isolated from a leukaemia patient. pKP2442 was mobilised by intragenus and intergenus transconjugation from the clinical isolate to Escherichia coli J53 (transconjugation frequency 6.86 × 10-8 ± 5.57 × 10-8) and K. pneumoniae PRZ (transconjugation frequency 4.04 × 10-8 ± 3.03 × 10-8), respectively. Since acquisition of resistance determinants often results in a loss of fitness, the impact of mcr-1 on the fitness of E. coli and K. pneumoniae was investigated. Escherichia coli J53 and K. pneumoniae PRZ transformants harbouring the TOPO expression vector encoding mcr-1 displayed significantly decreased growth rates compared with isogenic parental strains and controls. In contrast, competitive growth experiments revealed equal growth rates between E. coli J53 pKP2442 transconjugants (TcpKP2442) and the parental strain, whereas K. pneumoniae PRZ TcpKP2442 showed significantly reduced growth rates compared with their parental strain (selection rate constant -1.62 ± 0.49), indicating a decrease in fitness. Infection of A549 human lung epithelial cells with TcpKP2442 or mcr-1 transformants and controls revealed equal lactate dehydrogenase activities, indicating no significant impact of mcr-1 on cytotoxicity. Likewise, survival of Galleria mellonella larvae infected with mcr-1-expressing strains and isogenic controls was similar. These data indicate that expression of mcr-1 is able to cause a fitness cost when encoded on expression vectors and that acquisition of natural plasmid-borne mcr-1 does not impair fitness in E. coli J53 but negatively influences growth rates in K. pneumoniae PRZ.