Prevalence of hypervirulent and carbapenem-resistant Klebsiella pneumoniae under divergent evolutionary patterns

Abstract

K1/K2 hvKP strains acquire carbapenem-resistance plasmids, known as CR-hvKp, and carbapenem-resistant Klebsiella pneumoniae (CRKP) strains obtain virulence plasmids, recognized as hv-CRKP. The two different evolution patterns of hypervirulent combined carbapenem-resistant Klebsiella pneumoniae may lead to their different prevalence in hospitals. Our study aimed to investigate the prevalence of hv-CRKP and CR-hvKp strains and to analyze factors influencing their evolution and prevalence. We collected 890 K. pneumoniae genomes from GenBank and 530 clinical K. pneumoniae isolates from nine hospitals. Our study found that hv-CRKP strains were more prevalent than CR-hvKp strains and both were dominated by bla KPC-2 gene. The bla KPC-2 -carrying plasmids could mobilize non-conjugative virulence plasmids from hvKp strains to CRKP strains. The conserved oriT of virulence plasmids and the widespread of conjugative helper plasmids were potential factors for the mobilization of non-conjugative virulence plasmids. HvKp strains with KPC plasmid could hardly simultaneously exhibit hypervirulence and carbapenem resistance as CRKP strains with virulence plasmid, and we found that rfaH mutation reduced capsular synthesis and increased carbapenem resistance of the CR-hvKp strain. In summary, this study revealed that hv-CRKP strains were more suitable for survival in hospital settings than CR-hvKp strains and the widespread conjugative KPC-producing plasmids contributed to the emergence and prevalence of hv-CRKP strains.

The making of hypervirulent Klebsiella pneumoniae

“…The virulence plasmids themselves are usually non‐conjugative and therefore non‐self‐mobilizable. However, they could be mobilized or co‐transferred with the help of the self‐transferable incompatibility group F plasmids 84,231 . Due to the hypercapsule of HvKP itself, which could mask the fimbriae and hamper the conjugation, the second pathway may be more convenient.…”

“…Due to the hypercapsule of HvKP itself, which could mask the fimbriae and hamper the conjugation, the second pathway may be more convenient. Hv‐CRKP is far more prevalent than CR‐HvKP 84 . ST11 accounted for over 70.0% among CR‐HvKP/Hv‐CRKP strains 62 .…”

“… 69 , 83 As reported in the document, 62 521 K. pneumoniae strains were collected from GenBank as of May 13, 2020; Molecular combinations predicted 29 strains to be bla KPC ‐positive and hypervirulent, of which 7 were CR‐HvKP and 22 were Hv‐CRKP; 94 and 165 strains were HvKP and bla KPC ‐positive K. pneumoniae , respectively. As of May 31, 2021, 890 K. pneumoniae genomes from GenBank were analyzed, and 53 Hv‐CRKP and 17 CR‐HvKP strains were designated 84 ; 478 and 168 strains were CR‐KP and HvKP, respectively. Among another 530 clinical K. pneumoniae strains collected in Mainland China from January 2017 to February 2018, 28 and 6 were Hv‐CRKP and CR‐HvKP respectively 84 ; 227 and 171 were CR‐KP and HvKP, respectively, showing constituent ratios of 12.3% for Hv‐CRKP among CRKP and 3.5% for CR‐HvKP among HvKP.…”

“…As of May 31, 2021, 890 K. pneumoniae genomes from GenBank were analyzed, and 53 Hv‐CRKP and 17 CR‐HvKP strains were designated 84 ; 478 and 168 strains were CR‐KP and HvKP, respectively. Among another 530 clinical K. pneumoniae strains collected in Mainland China from January 2017 to February 2018, 28 and 6 were Hv‐CRKP and CR‐HvKP respectively 84 ; 227 and 171 were CR‐KP and HvKP, respectively, showing constituent ratios of 12.3% for Hv‐CRKP among CRKP and 3.5% for CR‐HvKP among HvKP. Such surveillance results suggest Hv‐CRKP is far more prevalent than CR‐HvKP.…”

“…However, they could be mobilized or co‐transferred with the help of the self‐transferable incompatibility group F plasmids. 84 , 231 Due to the hypercapsule of HvKP itself, which could mask the fimbriae and hamper the conjugation, the second pathway may be more convenient. Hv‐CRKP is far more prevalent than CR‐HvKP.…”