ompC/F mutations drive XDR phenotype and lineage defining super clones of E. coli: Sequential events and consequences

Multi-drug resistant Escherichia coli is an increasing public health problem. Though, PBP3 insertions with bla NDM , bla CMY and bla OXA-48 like is restricted to South-East Asia with few reports from USA. The study suggests omp C/F variants as a core factor to classify ESBL (E), non-ESBL (NE), and ESBL with PBP3 and carbapenemases (EPBP3) clones. EPBP3 results in treatment complication, as most of the time, E. coli with PBP3 insertions co-carries bla NDM (87.5%), bla CMY (96.3%) and bla OXA-48 like (88.8%) implicating it as a predisposing factor for carbapenemase gene acquirement. Cefiderocol and cefepime/zidebactam are the choice against EPBP3 E. coli . Evolutionary BEAST analysis revealed consecutive events of YRIN and YRIK insertions in PBP3 gene leading to a surge in MDR E. coli clones. Further, emergence of the super clones STs 410, 405, 167 and 617 featuring these phenotypes is a major threat for developing and developed countries, which needs close monitoring. Importance The manuscript describes various E. coli resistant genotypes across the globe and their importance in the choice of antimicrobial for treatment. The study identified six clades based on omp C and omp F mutations with a strong correlation to PBP3 insertions co-carried with beta-lactamases including bla NDM . Though, the omp C and omp F mutations were reported to precede the acquisition of carbapenemases in E. coli , clade segregation based on AMR genes as observed in this study reveals the omp C and omp F genes as a potential biomarker for AMR clade identification in E. coli . Currently, cefiderocol and cefepime/zidebactam seems to be the only choice to cover the AMR mechanism mediated by PBP3 insertions. Further, emergence of the super clones STs 410, 405, 167 and 617 featuring these PBP3 phenotypes is a major threat for developing and developed countries, which needs close monitoring.