A single Proteus mirabilis lineage from human and animal sources: a hidden reservoir of OXA-23 or OXA-58 carbapenemases in Enterobacterales

Abstract

In Enterobacterales, the most common carbapenemases are Ambler’s class A (KPC-like), class B (NDM-, VIM- or IMP-like) or class D (OXA-48-like) enzymes. This study describes the characterization of twenty-four OXA-23 or OXA-58 producing-Proteus mirabilis isolates recovered from human and veterinary samples from France and Belgium. Twenty-two P. mirabilis isolates producing either OXA-23 (n = 21) or OXA-58 (n = 1), collected between 2013 and 2018, as well as 2 reference strains isolated in 1996 and 2015 were fully sequenced. Phylogenetic analysis revealed that 22 of the 24 isolates, including the isolate from 1996, belonged to a single lineage that has disseminated in humans and animals over a long period of time. The blaOXA-23 gene was located on the chromosome and was part of a composite transposon, Tn6703, bracketed by two copies of IS15∆II. Sequencing using Pacbio long read technology of OXA-23-producing P. mirabilis VAC allowed the assembly of a 55.5-kb structure encompassing the blaOXA-23 gene in that isolate. By contrast to the blaOXA-23 genes, the blaOXA-58 gene of P. mirabilis CNR20130297 was identified on a 6-kb plasmid. The acquisition of the blaOXA-58 gene on this plasmid involved XerC-XerD recombinases. Our results suggest that a major clone of OXA-23-producing P. mirabilis is circulating in France and Belgium since 1996.

Genetic Diversity, Biochemical Properties, and Detection Methods of Minor Carbapenemases in Enterobacterales

“…Intriguingly, the genomes of 20 OXA-23-producing P. mirabilis isolates recovered from France and Belgium have been compared to all Proteus genomes available in the NCBI database. This study highlighted that all isolates belonged to a single lineage that has spread since 1996 ( 126 ). Moreover, veterinary samples were included in this study and revealed that this lineage has spread also in animals ( 126 ).…”

“…This study highlighted that all isolates belonged to a single lineage that has spread since 1996 ( 126 ). Moreover, veterinary samples were included in this study and revealed that this lineage has spread also in animals ( 126 ). Analysis of the genetic context revealed that the bla OXA−23 gene is mainly carried on the chromosome of P. mirabilis ( 122 , 124 , 127 ) except for one isolate from France and three isolates from Singapore.…”

“…Regarding the other isolates, the bla OXA−23 is carried by complex IS 26 -based transposon. However, it is always associated to IS Aba1 in its 5' extremity leading to its expression ( 126 ). OXA-23-producing P. mirabilis can be hard to detect.…”

“…A moderate increase of carbapenem MICs can be observed from 0.25 to 0.5 mg/L but the presence of this carbapenemase should be evocated mainly in case of an increase of MICs for amoxicillin-clavulanate combination ( Figure 3 ) ( 129 ). In addition to the difficulty to detect a phenotype associated to the production of OXA-23, most of carbapenemase detection tests for Enterobaterales do not detect carbapenem hydolyzing class D β-lactamases (CHDLs) other than OXA-48 ( 126 ).…”

Functional Analysis of the Acinetobacter baumannii XerC and XerD Site-Specific Recombinases: Potential Role in Dissemination of Resistance Genes

“…Among the genes found within these modules are bla OXA-58 ; the bla OXA-143 -like bla OXA-253 ; the tetracycline resistance gene tet39 ; the macrolide resistance genes msrE and mphE ; the chromium resistance genes chrA and chrB ; the organic hydroperoxide resistance genes ohr/ohrR ; the transport-related genes, such as sulP and kup ; the tellurium resistance terC ; and toxin-antitoxin ( add ) genes [ 19 , 23 , 26 , 29 , 30 , 31 ]. Some of them, like ohr/ohrR , chrA , chrB , sulP , kup , and add , were found in different Acinetobacter species [ 30 ], and bla OXA-58 was found in Proteus mirabilis [ 26 , 32 ].…”