The emergence of Highly Virulent Multidrug Resistant Klebsiella pneumoniae causing Urinary Tract Infections in Young Women in the Community

Urinary tract infection (UTI) is the most common bacterial infection in the community. The major pathogen causing community UTIs is Escherichia coli. However, in recent years with the increasing problem of antibiotic resistance, multidrug resistant (MDR) Klebsiella pneumoniae (Kpn) may emerge as a causative agent for community UTI. We aimed to explore the resistance patterns and virulence traits of Kpn, causing UTI in healthy young women in Israel.

Isolates were selected from a nationwide UTI collection. We focused on 19 Kpn isolates possessing an MDR profile (resistance to all cephalosporins and trimethoprim/sulfamethoxazole, 30% resistance to quinolones, and 80% non-susceptibility to nitrofurantoin). Isolate genotyping revealed genetically-non-related isolates. Molecular analysis identified the presence of mega plasmids encoding antibiotic resistance gene-cassettes, including extended-spectrum b-lactamase genes (CTX-M). Fitness experiments demonstrated that all isolates proliferate in the presence of artificial urine. Virulence assessment demonstrated variation in biofilm production and in the ability to survive human serum. In a Caenorhabditis elegans host-pathogen-model, all strains showed killing the ability of the nematodes (LT50 of approx. 6h) compared to a control E. coli OP50 strain. Complete sequencing of a representative MDR-encoding plasmid (Illumina and MinION) revealed a mega-plasmid encoding ten antibiotic resistance genes, wide-resistances to heavy-toxic-metals including copper and silver as well as the iron-transport system-fec, which suggests environmental superiority to the carrying bacteria.

These data demonstrate the emergence of highly-virulent MDR Kpn as a causative pathogen of community UTI and improves our understanding to optimize empiric therapy that should be implemented to treat these infections effectively.