Genomic Insights of Emerging Multidrug-Resistant OXA-48-Producing ST135 Proteus mirabilis

<b>Background/Objectives</b>: Among <i>Enterobacterales</i>, OXA-48-like-producing <i>Proteus mirabilis</i> strains have been scarcely detected. Herein, we characterized a <i>bla</i>_OXA-48-harbouring <i>P. mirabilis</i> strain recovered from Greece (Pm GR-1), while phylogenomics and comparative genomics analyses with previously published <i>bla</i>_OXA-48 carriers were also assessed. <b>Methods</b>: Characterization of Pm GR-1 was performed by the Vitek^® Compact and Mass Spectrometry systems, antimicrobial susceptibility testing, detection of beta-lactamases, multilocus-sequence typing (MLST), and whole-genome sequencing (WGS). In silico prediction of mobile genetic elements (MGEs), genomic islands (GIs), antimicrobial resistance genes (ARGs) and virulence factors (VFs), and phylogenetic, core-genome SNP and comparative genomics analyses were executed using bioinformatic tools. <b>Results</b>: Pm GR-1 was isolated from a urine sample of an outpatient in a Greek hospital. It exhibited a multidrug-resistant phenotype, being susceptible only to amikacin and ceftazidime/avibactam. It co-carried several beta-lactamase genes on the chromosome (<i>bla</i>_OXA-48, <i>bla</i>_CTX-M-14, <i>bla</i>_TEM-1) and a plasmid <i>(bla</i>_TEM-2) and several other ARGs, but also mutations associated with quinolone resistance in the DNA gyrase and topoisomerase IV subunits. It belonged to the international clone ST135 that has also been detected among OXA-48-producing <i>P. mirabilis</i> strains from Germany and the USA. Pm GR-1 was genetically related to those from Germany, sharing highly similar MGEs, GIs, ARGs and VFs, including the chromosomal <i>bla</i>_OXA-48 genetic structure, the O-antigen locus, the flagella locus, the MR/P fimbriae operon, and the urease gene cluster. <b>Conclusions</b>: To our knowledge, this is the first report from Greece of a <i>bla</i>_OXA-48-possessing <i>P. mirabilis</i> strain. The emergence of <i>bla</i>_OXA-48 among <i>P. mirabilis</i> strains of the international clone ST135 in different geographical regions is worrying. Close monitoring of these strains is required in One Health settings.