Abstract
BACKGROUND: Klebsiella pneumoniae continues to be a problem worldwide. This study aimed to elucidate the evolution of a K. pneumoniae strain from harbouring bla(KPC−2) to bla(KPC−90). METHODS: Three K. pneumoniae strains (Kpn_XM11, Kpn_XM12, and Kpn_XM13) belonging to the same clone were isolated from a patient, followed by identification, antimicrobial susceptibility test, whole genome sequencing, and gene mutations. RESULTS: Kpn_XM11 and Kpn_XM12 strains harbouring bla(KPC−2) were resistant to carbapenems but susceptible to ceftazidime-avibactam (CZA) while Kpn_XM13 possessing bla(KPC−90) was resistant to CZA but susceptible to imipenem. Compared to KPC-2, KPC-90 was a variant with an insertion of two amino acids (180 ins Tyr-Thr), which is structurally located between the α7 helix and α8 helix of KPC. The genetic structures of bla(KPC) in three strains were identified as IS26-ISKpn27-bla(KPC)-ISKpn6-IS26. Mutation of bla(KPC−2) into bla(KPC−90) in Kpn_XM11 conferred similar drug-resistance phenotype as that of Kpn_XM13. Deletion of bla(KPC−2) in Kpn_XM11 and bla(KPC−90) in Kpn_XM13 exerted susceptibility against CZA but retained carbapenem resistance. Kpn_XM11 to Kpn_XM13 possessed ompK35 but couldn’t yield OmpK35; in addition, they all presented R935H mutation in RecC. The plasmids carrying bla(KPC−2) or bla(KPC−90) could both be mated at ratios of a 10(− 8) level. CONCLUSIONS: It is of great concern that bla(KPC−2) may evolve into other subtypes, conferring distinguished drug-resistance phenotype, even before the use of CZA, which may be associated with R935H mutation in RecC. Advanced methods are essential under such conditions so as to find out slight nucleotide differences and control infections efficiently. GRAPHICAL ABSTRACT: [Image: see text]