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 Escherichia coli 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 bla NDM-5 and bla KPC-3 , and a series of additional β-lactamase genes, including bla CTX-M-15 and bla SHV-11 encoding extended-spectrum β-lactamases (ESBLs), bla CMY-145 encoding an AmpC-type cephalosporinase, and bla 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 E. coli isolate carried virulence factors ( sitA, gad, hra, terC , traT , and cia ) and many other non-β-lactam resistance determinants including rmtB , tet(A), dfrA17 (two copies), aadA1, aadA5 (two copies), sul1 (two copies), qacE (two copies), qepA , mdf(A) , catA1 , erm(B) , mph(A) , and qnrS1 , being susceptible only to tigecycline, colistin and fosfomycin. In conclusion, we described here the phenotypic and genome characteristics of an extensively drug-resistant (XDR) E. coli ST361 being recognized as an emerging clone worldwide.