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

Area of Science:

• Microbiology
• Genomics
• Antimicrobial Resistance

Background:

• OXA-48-like carbapenemase-producing Enterobacterales are a growing global health concern.
• Proteus mirabilis strains harboring OXA-48-like carbapenemases are rarely reported.
• Characterization of such strains is crucial for understanding their epidemiology and spread.

Purpose of the Study:

• To characterize a novel OXA-48-like carbapenemase-producing Proteus mirabilis strain (Pm GR-1) from Greece.
• To perform phylogenomic and comparative genomic analyses with other known OXA-48-like carbapenemase-producing strains.
• To assess the genetic relatedness, antimicrobial resistance, and virulence factors of the identified strain.

Main Methods:

• Phenotypic and biochemical characterization using Vitek® Compact and Mass Spectrometry.
• Antimicrobial susceptibility testing and beta-lactamase detection.
• Multilocus Sequence Typing (MLST) and Whole-Genome Sequencing (WGS).
• In silico analysis of mobile genetic elements (MGEs), genomic islands (GIs), antimicrobial resistance genes (ARGs), and virulence factors (VFs).
• Phylogenetic, core-genome SNP, and comparative genomic analyses.

Main Results:

• The Pm GR-1 strain, isolated from a Greek hospital outpatient urine sample, exhibited multidrug resistance, susceptible only to amikacin and ceftazidime/avibactam.
• It harbored multiple beta-lactamase genes (blaOXA-48, blaCTX-M-14, blaTEM-1, blaTEM-2) and other ARGs, alongside quinolone resistance mutations.
• The strain belonged to international clone ST135 and showed genetic similarity to OXA-48-producing P. mirabilis strains from Germany and the USA, sharing key genetic structures and virulence factors.

Conclusions:

• This study represents the first report of a blaOXA-48-possessing Proteus mirabilis strain in Greece.
• The emergence and spread of blaOXA-48 in P. mirabilis strains of international clone ST135 across different regions is a significant public health concern.
• Continuous surveillance of these strains within One Health frameworks is essential to mitigate their impact.