OXA-48-like carbapenemases in Proteus mirabilis - novel genetic environments and a challenge for detection

Emerg Microbes Infect. 2024 Dec;13(1):2353310. doi: 10.1080/22221751.2024.2353310. Epub 2024 May 23.

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.

Keywords: OXA-162; OXA-181; OXA-48; Proteus mirabilis; carbapenemase-producing Enterobacterales.

MeSH terms

  • Anti-Bacterial Agents* / pharmacology
  • Bacterial Proteins* / genetics
  • Bacterial Proteins* / metabolism
  • Carbapenems / pharmacology
  • Genomic Islands
  • Humans
  • Microbial Sensitivity Tests*
  • Plasmids / genetics
  • Proteus Infections* / microbiology
  • Proteus mirabilis* / drug effects
  • Proteus mirabilis* / enzymology
  • Proteus mirabilis* / genetics
  • Proteus mirabilis* / isolation & purification
  • beta-Lactamases* / genetics
  • beta-Lactamases* / metabolism

Substances

  • beta-Lactamases
  • Bacterial Proteins
  • Anti-Bacterial Agents
  • carbapenemase
  • Carbapenems