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Host-dependent effects of mcr-1 and mcr-8 on fitness; virulence; and transmission in Escherichia coli and Klebsiella pneumoniae
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DOI：10.3389/fmicb.2026.1908233.png)
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Abstract
En 中文
IntroductionAs 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.MethodsThis 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.ResultsOur 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.DiscussionOur 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.
Keywords:
virulence
Enterobacterales
host specificity
fitness cost
mcr-1
mcr-8
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