Genomic characterization of carbapenemase-producing Klebsiella pneumoniae ST307 revealed multiple introductions in Buenos Aires, Argentina.

OBJECTIVE: to describe at genomic level nine carbapenemase-producing Klebsiella pneumoniae ST307 (Kp-ST307) clinical isolates recovered in Buenos Aires during 2017-2021, investigating their resistome, virulome and phylogeny.

METHODS: Antimicrobial susceptibility was determined according to CLSI. Genomic DNA was sequenced by Illumina MiSeq and analyzed using SPAdes, PROKKA and Kleborate. Phylogeny of 355 randomly selected Kp-ST307 genomes and those from nine local isolates was inferred by a maximum-likelihood approach. The tree was visualized using Microreact.

RESULTS: Besides resistance to ß-lactams and fluoroquinolones, six out of nine Kp-ST307 were also resistant to ceftazidime/avibactam (CZA). This difficult-to-treat resistance phenotype was mediated by blaSHV-28 and gyrA-83I/parC-80I mutations in addition to carbapenemase coding genes. Among CZA susceptible isolates, two of them harbored blaKPC-3 while the other harbored blaKPC-2 +blaCTX-M-15 . Respect to CZA resistant isolates, three harbored blaKPC-3 +blaNDM-1 +blaCMY-6 , two carried blaKPC-2 +blaNDM-5 +blaCTX-M-15 , and blaNDM-5 +blaCTX-M-15 were detected in the remaining isolate. Besides, five colistin resistant isolates presented a nonsense mutation in mgrB. Global Kp-ST307 isolates were distributed in two deep-branching lineages while local isolates set in the main clade of the phylogenetic tree. The five isolates from a same hospital, harboring blaKPC-3 or blaKPC-3 +blaNDM-1+ blaCMY-6 , clustered in a monophyletic subclade with Italian isolates. Also, an isolate harboring blaKPC-2 +blaNDM-5 +blaCTX-M-15 recovered in another hospital was closed to this group. The remaining local Kp-ST307 grouped in other subclades containing isolates of diverse geographically origin.

CONCLUSION: The inferred resistome was consistent with the resistant phenotype. Phylogeny suggested multiple introduction events in our region and a single major introduction in one hospital followed by local spread.