Genomic Characterization of an Extensively Drug-Resistant Extra-Intestinal Pathogenic (ExPEC) Escherichia coli Clinical Isolate Co-Producing Two Carbapenemases and a 16S rRNA Methylase

An extensively drug-resistant <i>Escherichia coli</i> clinical isolate (N1606) belonging to Sequence Type 361 was recovered from the urine of a patient hospitalized in Switzerland. The strain showed resistance to virtually all β-lactams including the latest generation antibiotics cefiderocol and aztreonam-avibactam. Whole genome sequencing revealed that it possessed two carbapenemase-encoding genes, namely <i>bla</i>_NDM-5 and <i>bla</i>_KPC-3, and a series of additional β-lactamase genes, including <i>bla</i>_CTX-M-15 and <i>bla</i>_SHV-11 encoding extended-spectrum β-lactamases (ESBLs), <i>bla</i>_CMY-145 encoding an AmpC-type cephalosporinase, and <i>bla</i>_OXA-1 encoding a narrow-spectrum class D ß-lactamase. Most of these resistance genes were located on plasmids (IncFII-FIA, IncX3, IncIγ, IncFII). That strain exhibited also a four amino-acid insertion in its penicillin-binding protein 3 (PBP3) sequence, namely corresponding to YRIN. Complete genome analysis revealed that this <i>E. coli</i> isolate carried virulence factors (<i>sitA, gad, hra, terC</i>, <i>traT</i>, and <i>cia</i>) and many other non-β-lactam resistance determinants including <i>rmtB</i>, <i>tet(A), dfrA17</i> (two copies), <i>aadA1, aadA5</i> (two copies), <i>sul1</i> (two copies), <i>qacE</i> (two copies), <i>qepA</i>, <i>mdf(A)</i>, <i>catA1</i>, <i>erm(B)</i>, <i>mph(A)</i>, and <i>qnrS1</i>, being susceptible only to tigecycline, colistin and fosfomycin. In conclusion, we described here the phenotypic and genome characteristics of an extensively drug-resistant (XDR) <i>E. coli</i> ST361 being recognized as an emerging clone worldwide.