Emergence and Evolution of Unique Plasmids Harboring blaIMP-70 and blaCTX-M-253 in Multidrug-Resistant Providencia rettgeri

Abstract

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.

Keywords: CTX-M-253; IMP-70; Providencia rettgeri; multidrug-resistant Enterobacterales; plasmid; β-lactamase.