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Background <p><i>Klebsiella pneumoniae</i> continues to be a problem worldwide. This study aimed to elucidate the evolution of a <i>K. pneumoniae</i> strain from harbouring <i>bla</i><sub>KPC−2</sub> to <i>bla</i><sub>KPC−90</sub>.</p> Methods <p>Three <i>K. pneumoniae</i> 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.</p> Results <p>Kpn_XM11 and Kpn_XM12 strains harbouring <i>bla</i><sub>KPC−2</sub> were resistant to carbapenems but susceptible to ceftazidime-avibactam (CZA) while Kpn_XM13 possessing <i>bla</i><sub>KPC−90</sub> 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 <i>bla</i><sub>KPC</sub> in three strains were identified as IS26-ISKpn27-<i>bla</i><sub>KPC</sub>-ISKpn6-IS26. Mutation of <i>bla</i><sub>KPC−2</sub> into <i>bla</i><sub>KPC−90</sub> in Kpn_XM11 conferred similar drug-resistance phenotype as that of Kpn_XM13. Deletion of <i>bla</i><sub>KPC−2</sub> in Kpn_XM11 and <i>bla</i><sub>KPC−90</sub> in Kpn_XM13 exerted susceptibility against CZA but retained carbapenem resistance. Kpn_XM11 to Kpn_XM13 possessed <i>ompK35</i> but couldn’t yield OmpK35; in addition, they all presented R935H mutation in RecC. The plasmids carrying <i>bla</i><sub>KPC−2</sub> or <i>bla</i><sub>KPC−90</sub> could both be mated at ratios of a 10<sup>− 8</sup> level.</p> Conclusions <p>It is of great concern that <i>bla</i><sub>KPC−2</sub> 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.</p> Graphical Abstract <p></p>

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Shifting of blaKPC−2 to blaKPC−90 in a sequence type 11 Klebsiella pneumoniae strain before the use of ceftazidime-avibactam

  • 期刊论文

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  • 发表日期：

    2026年2月19日

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  • Dakang Hu,
  • Yuanxun Zhao,
  • Shuli Mi,
  • Shijie Wang,
  • Jin Zhang,
  • Xinhua Luo,
  • Dan Li,
  • Jin Chen,
  • Guolin Hong

摘要

Background

Klebsiella pneumoniae continues to be a problem worldwide. This study aimed to elucidate the evolution of a K. pneumoniae strain from harbouring blaKPC−2 to blaKPC−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 blaKPC−2 were resistant to carbapenems but susceptible to ceftazidime-avibactam (CZA) while Kpn_XM13 possessing blaKPC−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 blaKPC in three strains were identified as IS26-ISKpn27-blaKPC-ISKpn6-IS26. Mutation of blaKPC−2 into blaKPC−90 in Kpn_XM11 conferred similar drug-resistance phenotype as that of Kpn_XM13. Deletion of blaKPC−2 in Kpn_XM11 and blaKPC−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 blaKPC−2 or blaKPC−90 could both be mated at ratios of a 10− 8 level.

Conclusions

It is of great concern that blaKPC−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