Comparative genomic analysis of extensively drug-resistant Proteus mirabilis co-producing VIM-1 and OXA-48...

Recent reports indicate a rise in multidrug-resistant (MDR) Proteus mirabilis in One Health settings, yet global data on its molecular epidemiology remains limited. Herein, an extensively drug-resistant (XDR) P. mirabilis strain was analyzed to determine its genomic make-up and evolutionary history.

A clinical isolate, designated Pm GR-164, was consistently recovered from pus specimens obtained from a patient hospitalized at a tertiary care hospital in Athens, Greece. Identification, antimicrobial susceptibility testing, carbapenemase content determination by lateral flow immunoassay and PCR, multilocus-sequence typing, and whole-genome sequencing were performed. Bioinformatic tools were used for prediction of antimicrobial resistance genes, virulence factors, mobile genetic elements, phage sequences, and chromosomal mutations conferring resistance to quinolones. Comparative genomics of the carbapenemase-carrying structures and phylogenomic analyses were also conducted.

Pm GR-164 exhibited an XDR phenotype, and its genomic analysis revealed the presence of several acquired antimicrobial resistance, virulence, and phage genes on its chromosome, and one plasmid. The bla_VIM-1 gene and the bla_OXA-48/bla_CTX-M-14-carrying module were located at different chromosomal loci, indicating separate integration events. Mutations in the GyrA, GyrB and ParC subunits were also identified. Pm GR-164 was assigned to ST269, showing a closer phylogenomic relatedness to MDR ST269 strains from Germany compared to those from the USA and UK.

This study expands the understanding of the dissemination of MDR P. mirabilis strains. Continuous global genomic surveillance is essential to monitor the emergence and dissemination of XDR P. mirabilis ST269 strains co-producing VIM-1 and OXA-48 carbapenemases, and to characterize the associated genetic structures.