MCR Expression Conferring Varied Fitness Costs on Host Bacteria and Affecting Bacteria Virulence

Area of Science:

• Antimicrobial Resistance
• Molecular Biology
• Evolutionary Genetics

Background:

• The emergence of plasmid-mediated colistin resistance genes (mcr) poses a significant threat to public health.
• Nine mcr genes (mcr-1 to mcr-10) and their variants have been identified, exhibiting diverse distribution patterns.
• Understanding the evolutionary advantages and fitness costs associated with different mcr genes is crucial for predicting their spread.

Purpose of the Study:

• To compare the effects of expressing different MCR proteins (MCR-1 to MCR-5) on bacterial fitness and virulence.
• To investigate the evolutionary advantages conferred by MCR-1 compared to other MCR variants.

Main Methods:

• Comparative analysis of bacterial growth and survival in the presence of colistin.
• LIVE/DEAD staining to assess bacterial membrane integrity and fitness burden.
• In vitro trans-well assay for epithelial penetration and in vivo Galleria mellonella model for virulence assessment.

Main Results:

• MCR-1 expressing strains exhibited superior growth in colistin compared to MCR-2 to MCR-5 expressing strains.
• MCR-3 to MCR-5 imposed greater fitness costs on bacteria than MCR-1 and MCR-2.
• Expression of MCRs (except MCR-2) enhanced bacterial virulence, increasing epithelial penetration and survival in Galleria mellonella, potentially via membrane damage and LPS release.

Conclusions:

• MCR-1 confers the highest survival advantage among the tested MCRs, likely contributing to its widespread dissemination.
• MCR expression can increase bacterial virulence, raising concerns for infectious disease control.
• Further research and surveillance are necessary to manage the spread of mcr-carrying pathogens.