Genomic Insights into a Multidrug-Resistant Escherichia coli of sequence type 155: A Ceftazidime-Avibactam Resistant Strain Harboring Four Classes of β-Lactamases

•Identified a multidrug-resistant E. coli strain co-producing β-lactamases from all four Ambler classes.•Discovered a chimeric plasmid, pQMM-2-NDM-5, harboring the blaNDM-5 gene with broad antibiotic resistance.•Revealed intercontinental transmission pathways for resistance genes linked to poultry farming.•Utilized dual-platform whole-genome sequencing for comprehensive resistance profiling.•Highlighted the critical need for global antibiotic stewardship to combat resistance spread. : The emergence of multidrug-resistant (MDR) Escherichia coli strains has significantly constrained antibiotic treatment options, while the spread of antimicrobial resistance genes (ARGs) and mobile genetic elements exacerbates the situation. This study delves into an MDR E. coli strain, QMM-01, which uniquely co-expresses β-lactamases from all four recognized classes, aiming to uncover the underlying mechanisms of its resistance and assess its potential for global spread. :E. coli QMM-01, isolated from a burn patient, underwent antibiotic susceptibility testing through standard automated procedures commonly employed in clinical settings, with further test by immunochromatographic tests for carbapenemases. For genomic insights, whole-genome sequencing (WGS) was performed using both PacBio Sequel and Illumina NovaSeq platforms, supplemented by bioinformatics analyses to predict antimicrobial resistance genes, determining serotypes, performing multilocus sequence typing, and conducting comparative genomic analysis. : QMM-01 exhibited resistance to a broad spectrum of β-lactam antibiotics, including carbapenems and ceftazidime-avibactam, with aztreonam being the sole exception. The resistance profile of the strain might primarily be due to the production of class B metallo-β-lactamases. WGS revealed the presence of a chimeric plasmid, pQMM-2-NDM-5, carrying the blaNDM-5 gene and exhibiting similarities with plasmids from diverse geographical regions. This plasmid contains 161 predicted coding sequences and harbors resistance genes for 13 different antibiotics, forming a resistance island with a complex genetic environment. : This study underscores the global challenge posed by antibiotic resistance and emphasizes the need for international collaboration in antibiotic stewardship to mitigate the spread of resistance genes.