Host-dependent effects of mcr-1 and mcr-8 on fitness, virulence, and transmission in Escherichia coli and Klebsiella pneumoniae

Abstract

Introduction As one of the most common groups of clinical pathogens, Enterobacterales pose a serious threat to global public health due to their multidrug-resistance. Polymyxin serves as a last-line treatment for infections caused by Carbapenem-resistant Enterobacterales (CRE). The emergence and spread of the mobilized colistin resistance (mcr) genes, particularly the globally prevalent mcr-1 and mcr-8, have raised significant public health concerns. Epidemiological data reveal a striking host tropism among these genes: mcr-1 is predominantly found in Escherichia coli (83.75%), while mcr-8 is primarily detected in Klebsiella pneumoniae (92.68%). The underlying mechanisms driving this host-specific distribution and its implications for bacterial virulence remain poorly understood. Methods This study investigated the host-dependent fitness, transmission, and virulence effects of mcr-1 and mcr-8 using a combination of recombinant plasmids transformed into E. coli DH5α and K. pneumoniae ATCC 13883, alongside clinical isolates. Results Our results demonstrate that the biological cost and benefit associated with these plasmids are host-dependent. In K. pneumoniae, the mcr-8 plasmid exhibited enhanced stability and fitness. Conversely, the mcr-1 plasmid conferred a competitive advantage in E. coli. The impact on bacterial virulence in Galleria mellonella larvae infection model varied with the host strain. Discussion Our findings indicate that the fitness, transmission potential, and virulence modulation conferred by mcr-1 and mcr-8 are closely associated with the bacterial host. Specifically, the mcr-1 plasmid exhibits enhanced transmissibility in E. coli compared to K. pneumoniae, whereas the mcr-8 plasmid demonstrates a transmission advantage in K. pneumoniae over E. coli. The findings of this study clarify that the preferred hosts of mcr-1 and mcr-8 plasmids are E. coli and K. pneumoniae, respectively, and confirm that plasmid fitness, transmissibility, and virulence effects are host-dependent. These results suggest that future development of prevention and control strategies should incorporate differentiated interventions targeting distinct bacterial hosts and plasmid types, in order to more effectively curb the spread of mcr genes and extend the clinical utility of polymyxin.