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Dissemination of blaOXA-58 in Proteus mirabilis isolates from Germany
Felix Lange1, Niels Pfennigwerth1, Sonja Gerigk2
1Department of Medical Microbiology, Ruhr-University Bochum, Universitätsstraße 150, Bochum, 44801, Germany.
Objectives:
Characterization of Proteus mirabilis isolates harbouring bla OXA-58 with emphasis on the genetic environment of this resistance determinant.
Methods:
Strains of P. mirabilis ( n = 37) isolated from different patients were tested for the presence of bla OXA-58 . The genetic context of bla OXA-58 was determined by WGS of two strains and Sanger sequencing. Clonality of the strains was assessed by PFGE. Susceptibility testing was performed by microdilution according to EUCAST.
Results:
Four strains isolated in different geographical regions of Germany were positive for bla OXA-58 , and WGS showed that this resistance gene was harboured on a plasmid. Sanger sequencing confirmed the presence of two nearly identical plasmids, 6219 and 6208 bp in size, in all four strains. Upstream of bla OXA-58 an IS Aba 3-like transposase gene was located. The P. mirabilis strains were not clonally related according to PFGE. MICs of meropenem for three of the strains were only just above the EUCAST breakpoint and the Carba NP test was positive for only two of the strains.
Conclusions:
To our knowledge, this is the first description of bla OXA-58 in the species P. mirabilis . The resistance gene is harboured by almost identical plasmids in strains not clonally related and from different geographical regions. Apart from an IS Aba 3-like transposase gene upstream of bla OXA-58 the genetic context is different from bla OXA-58 harboured on plasmids in the genus Acinetobacter . With MICs of meropenem well below the EUCAST breakpoint or only just above it and equivocal or false negative results from the Carba NP test, bla OXA-58 can be easily overlooked in P. mirabilis .
Insights
This study identifies the bla OXA-58 gene in Proteus mirabilis strains, finding it on similar plasmids across different regions. This carbapenemase can be easily missed in P. mirabilis due to low meropenem MICs.
Area of Science:
- Microbiology
- Genetics
- Antimicrobial Resistance
Background:
- Carbapenemase-producing Enterobacterales (CPE) are a significant global health threat.
- Proteus mirabilis is a common opportunistic pathogen, but carbapenem resistance is rarely reported.
- The bla OXA-58 gene encodes a carbapenemase primarily found in Acinetobacter species.
Purpose of the Study:
- To characterize Proteus mirabilis isolates carrying the bla OXA-58 gene.
- To investigate the genetic environment and plasmid context of bla OXA-58 in P. mirabilis.
- To assess the susceptibility profiles and diagnostic implications of bla OXA-58 in P. mirabilis.
Main Methods:
- Whole-genome sequencing (WGS) and Sanger sequencing were used to determine the genetic context of bla OXA-58.
- Pulsed-field gel electrophoresis (PFGE) was employed to assess strain clonality.
- Antimicrobial susceptibility testing (AST) was performed using microdilution according to EUCAST guidelines, and Carba NP testing was conducted.
Main Results:
- Four P. mirabilis strains from different German regions harbored bla OXA-58 on nearly identical plasmids (6219 and 6208 bp).
- An IS Aba 3-like transposase gene was located upstream of bla OXA-58.
- The P. mirabilis strains were not clonally related, and meropenem MICs were borderline or below EUCAST breakpoints, with variable Carba NP test results.
Conclusions:
- This is the first report of bla OXA-58 in Proteus mirabilis, carried on similar plasmids in non-clonal strains from diverse locations.
- The genetic environment of bla OXA-58 in P. mirabilis differs from that observed in Acinetobacter species.
- The low meropenem MICs and potential for false-negative Carba NP tests highlight the risk of overlooking bla OXA-58 in P. mirabilis infections.
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