Emergence and Evolution of Unique Plasmids Harboring bla(IMP-70) and bla(CTX-M-253) in Multidrug-Resistant Providencia rettgeri

Although the prevalence of carbapenem-resistant Enterobacterales remains low in Japan, these bacteria are a growing problem worldwide, owing to their multidrug resistance phenotype. We isolated a multidrug-resistant Providencia rettgeri strain, NR1418, harboring a rare bla(IMP) variant, bla(IMP-70), a novel bla(CTX-M) variant, designated bla(CTX-M-253), and bla(MOX-1). This strain is resistant to β-lactams, amikacin, levofloxacin, and colistin. Genomic analysis revealed that NR1418 carries two plasmids, designated pNR1418-1 and pNR1418-2. The pNR1418-1 plasmid harbors bla(CTX-M-253), bla(TEM-1), and bla(MOX-1), while the pNR1418-2 plasmid harbors bla(IMP-70), which is located in a class 1 integron. Both plasmids exhibit high similarities with the plasmid of the P. rettgeri isolate BML2526, which also harbors bla(IMP-70) and was identified in the same region of Japan as NR1418 at a different point in time. This indicates the possibility of the emergence and evolution of IMP-70-producing P. rettgeri and suggests that the plasmid of BML2526 may have occurred following recombination of the two plasmids harbored by NR1418. Further, bla(IMP-70) and bla(CTX-M-253) were found on unique plasmids, indicating that they likely evolved through mutations and recombination. IMPORTANCE Although Providencia rettgeri is an opportunistic pathogen, its intrinsic resistance to colistin and tigecycline makes the treatment of carbapenem-resistant P. rettgeri challenging. We isolated a multidrug-resistant P. rettgeri strain which harbored a rare bla(IMP) variant, bla(IMP-70), a novel bla(CTX-M) variant, bla(CTX-M-253), and bla(MOX-1) from a urinary sample obtained in Osaka, Japan. We investigated its genetic structure and evaluated the evolution of the plasmids carrying these genes. We show that bla(IMP-70), bla(CTX-M-253), and bla(MOX-1) are present on unique plasmids and that they have high similarities to the plasmid of another IMP-70-producing P. rettgeri isolate that was identified as being from the same location. The evolution of plasmids through mutations and recombination may play a role in the development and spread of multidrug resistance.