Genomic characterization of IncC plasmid-mediated triple carbapenemase-producing Providencia hangzhouensis ST222

Providencia hangzhouensis is a recently described species within the Providencia genus that is most closely related to Providencia rettgeri and is infrequently isolated from human infections. Its clinical relevance and epidemiology remain poorly understood. Here, we describe two P. hangzhouensis isolates recovered from urine specimens from two epidemiologically linked adult patients. Carbapenemase production in both isolates was determined using the modified carbapenem inactivation method. The presence of carbapenem resistance genes, bla NDM-1 , bla KPC-2 and bla VIM-24 , was identified by multiplex real-time PCR and whole-genome sequencing. Both isolates belong to the novel ST222 and carry all three carbapenem resistance genes on an IncC plasmid. Genetic environment analysis revealed complex integration of mobile genetic elements; notably, bla NDM-1 was localized within the variable region of an insertion sequence common region 1 element, bla KPC-2 was located within a putative Tn3-like transposon and bla VIM-24 was identified as a gene cassette within a second class 1 integron. Epidemiological data uncovered evidence of horizontal transfer of the IncC plasmid involving a Citrobacter freundii ST185 isolate. The convergence of multiple antimicrobial resistance genes, including those conferring resistance to last-line antimicrobials, underscores the potential threat posed by this emerging drug-resistant pathogen.