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OXA-48-like carbapenemases in Proteus mirabilis - novel genetic environments and a challenge for detection
Janko Sattler1,2,3, Janina Noster2, Yvonne Stelzer2
1Institute for Medical Microbiology, Immunology and Hygiene, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany.
Abstract:
OXA-48-like enzymes represent the most frequently detected carbapenemases in Enterobacterales in Western Europe, North Africa and the Middle East. In contrast to other species, the presence of OXA-48-like in Proteus mirabilis leads to an unusually susceptible phenotype with low MICs for carbapenems and piperacillin-tazobactam, which is easily missed in the diagnostic laboratory. So far, there is little data available on the genetic environments of the corresponding genes, blaOXA-48-like, in P. mirabilis. In this study susceptibility phenotypes and genomic data of 13 OXA-48-like-producing P. mirabilis were investigated (OXA-48, n = 9; OXA-181, n = 3; OXA-162, n = 1). Ten isolates were susceptible to meropenem and ertapenem and three isolates were susceptible to piperacillin-tazobactam. The gene blaOXA-48 was chromosomally located in 7/9 isolates. Thereof, in three isolates blaOXA-48 was inserted into a P. mirabilis genomic island. Of the three isolates harbouring blaOXA-181 one was located on an IncX3 plasmid and two were located on a novel MOBF plasmid, pOXA-P12, within the new transposon Tn7713. In 5/6 isolates with plasmidic location of blaOXA-48-like, the plasmids could conjugate to E. coli recipients in vitro. Vice versa, blaOXA-48-carrying plasmids could conjugate from other Enterobacterales into a P. mirabilis recipient. These data show a high diversity of blaOXA-48-like genetic environments compared to other Enterobacterales, where genetic environments are quite homogenous. Given the difficult-to-detect phenotype of OXA-48-like-producing P. mirabilis and the location of blaOXA-48-like on mobile genetic elements, it is likely that OXA-48-like-producing P. mirabilis can disseminate, escape most surveillance systems, and contribute to a hidden spread of OXA-48-like.
Insights
OXA-48-like enzymes in Proteus mirabilis present a challenging diagnostic phenotype due to low carbapenem MICs. Their diverse genetic environments on mobile elements suggest potential for widespread dissemination and undetected spread.
Area of Science:
- Molecular biology
- Microbiology
- Genetics
Background:
- OXA-48-like carbapenemases are prevalent in Enterobacterales in specific global regions.
- Proteus mirabilis expressing OXA-48-like enzymes exhibits an atypical susceptible phenotype, complicating laboratory detection.
- Limited data exists on the genetic context of blaOXA-48-like genes within P. mirabilis.
Purpose of the Study:
- To investigate the susceptibility profiles and genomic characteristics of OXA-48-like-producing P. mirabilis isolates.
- To explore the genetic environments and mobile genetic elements associated with blaOXA-48-like genes in P. mirabilis.
- To assess the potential for dissemination of OXA-48-like carbapenemases via P. mirabilis.
Main Methods:
- Phenotypic analysis of antimicrobial susceptibility testing for 13 OXA-48-like-producing P. mirabilis isolates.
- Whole-genome sequencing and analysis to determine the genetic location and context of blaOXA-48-like genes.
- Conjugation experiments to evaluate the transferability of plasmids carrying blaOXA-48-like genes.
Main Results:
- Most isolates showed susceptibility to carbapenems (meropenem, ertapenem) and piperacillin-tazobactam, consistent with a difficult-to-detect phenotype.
- The blaOXA-48-like genes were found in diverse genetic locations, including chromosomal integration into genomic islands and carriage on various plasmids (IncX3, novel MOBF).
- Plasmid-mediated blaOXA-48-like genes demonstrated transmissibility via conjugation to E. coli recipients and could be acquired by P. mirabilis.
Conclusions:
- OXA-48-like-producing P. mirabilis exhibits significant genetic diversity in the location of blaOXA-48-like genes, contrasting with homogeneity in other Enterobacterales.
- The presence of blaOXA-48-like on mobile genetic elements in P. mirabilis facilitates potential dissemination.
- The combination of a cryptic phenotype and mobile genetic elements suggests OXA-48-like-producing P. mirabilis could contribute to a hidden spread of carbapenem resistance, evading surveillance systems.
