This article first reports the OXA-48-positive Proteus mirabilis clinical isolate GR-1 in Greece, which exhibits multidrug resistance and remains susceptible only to amikacin and ceftazidime/avibactam. Through whole-genome sequencing and comparative genomics analysis, the study identifies resistance genes including blaOXA-48, blaCTX-M-14, and blaTEM-1, along with abundant mobile genetic elements and genomic islands. The strain shows high homology with ST135 P. mirabilis strains from Germany and the US, suggesting international clonal dissemination. The work provides critical genomic insights for monitoring multidrug-resistant pathogens within the One Health framework.
Literature Overview
This article published in 'Antibiotics' reviews the genomic characteristics of the P. mirabilis GR-1 strain isolated from outpatient urine samples in Greece and its genetic relationship with the international ST135 clone. The strain demonstrates resistance to multiple antibiotics while remaining susceptible to amikacin and ceftazidime/avibactam. It carries β-lactamase genes (blaOXA-48, blaCTX-M-14, blaTEM-1) and chromosomal mutations associated with quinolone resistance. Comparative genomic analysis reveals high similarity with OXA-48-positive P. mirabilis strains from Germany and the US in terms of resistance genes, genomic islands, and virulence factors.
Background Knowledge
Proteus mirabilis is a significant opportunistic pathogen commonly associated with urinary tract infections, particularly in patients with long-term indwelling catheters. Its clinical importance has increased due to rapid development of antimicrobial resistance, especially carbapenem resistance. OXA-48 carbapenemases, known for hydrolyzing carbapenems through blaOXA-48 genes, are widely studied in Enterobacterales. However, blaOXA-48 in P. mirabilis is rare and often chromosomally integrated, with its transmission mechanism remaining unclear compared to plasmid-mediated spread. This study first identifies the ST135 P. mirabilis clone carrying blaOXA-48 in Greece, showing high homology with German and US isolates, suggesting potential global dissemination. The strain also harbors multiple virulence factors including O antigen, flagella, MR/P fimbriae, and urease gene clusters, critical for bacterial pathogenicity. The work provides new genomic evidence for OXA-48 resistance gene transmission patterns, genetic environments, and public health implications in P. mirabilis.
Research Methods and Experiments
The Pm GR-1 strain was isolated from outpatient urine samples at a tertiary hospital in Athens. Vitek® Compact system and mass spectrometry identified the strain, while antimicrobial susceptibility testing used broth microdilution. β-lactamase detection employed lateral flow immunochromatography. Molecular typing and genomic analysis utilized multilocus sequence typing (MLST) and whole-genome sequencing (WGS). Bioinformatics tools (MOB-suite, Island Viewer, BLASTn) predicted mobile genetic elements, genomic islands, antimicrobial resistance genes, and virulence factors. Phylogenetic tree construction and core-genome SNP analysis evaluated genetic relationships between Pm GR-1 and published OXA-48-positive P. mirabilis strains.
Key Conclusions and Perspectives
Research Significance and Prospects
This study provides the first report of OXA-48-producing P. mirabilis in Greece, highlighting potential global spread of blaOXA-48 through chromosomal integration mechanisms. Whole-genome sequencing proves essential for clinical identification due to possible evasion from conventional detection methods. Future efforts should focus on surveillance across clinical, environmental, and animal sources to evaluate transmission risks within the One Health framework. Additionally, the identified virulence factors and regulatory sRNA elements offer potential targets for antimicrobial therapies and gene expression studies, with further research on these elements providing therapeutic insights.
Conclusion
This work first documents the blaOXA-48-carrying P. mirabilis GR-1 strain in Greece, identified as part of the international ST135 clone. The strain exhibits multidrug resistance alongside blaCTX-M-14 and blaTEM-1 β-lactamase genes, plus chromosomal mutations conferring quinolone resistance. Genomic analysis reveals conserved virulence factors (O antigen, flagella, MR/P fimbriae, urease gene cluster) matching German and UK strains, including regulatory sRNA elements. Findings suggest blaOXA-48 transmission in P. mirabilis may occur through chromosomal integration or mobile element mechanisms. Future monitoring of resistance genes in this pathogen is crucial to prevent clinical spread. The study provides genomic resources for investigating OXA-48 resistance mechanisms and establishes foundations for rapid pathogen identification and virulence factor regulation research.
