Convergence of plasmid-driven virulence and antibiotic resistance in Escherichia coli.

Plasmids are major vehicles for the spread of antibiotic resistance genes. Some plasmids additionally carry virulence genes that enhance host pathogenicity. The convergence of resistance and virulence genes on the same plasmid poses significant risk, providing a mechanism to create pathogens that cause severe disease with limited treatment options. Colicin V (ColV)-like plasmids (ColVLPs) are virulence plasmids frequently carried by extra-intestinal pathogenic E. coli (ExPEC) that cause human and avian infection. Here, by generating and analysing a ColVLP database, we demonstrate that ColVLPs form four distinct sub-groups, characterised by genes encoding for Colicins V and M, with differing virulence and antimicrobial resistance gene carriage. Three of these sub-groups possess moderate-high resistance towards multiple antibiotic classes. We further describe ColVLP co-integrates that have acquired extensive resistance profiles, including against last line colistin, through recombination with co-resident plasmids. Using pMS7163A, a ColVLP from a virulent ExPEC strain, we also demonstrate that the ColVLP-encoded outer membrane protease virulence factor OmpTp works co-operatively with its chromosomal homolog to enhance ExPEC resistance against human cathelicidin (LL-37), an antimicrobial peptide expressed in the urinary tract. Together, our work characterises ColVLPs as high-risk mobile genetic elements that amplify the convergence of resistance and virulence in ExPEC.