Characteristics of Hypervirulent Klebsiella pneumoniae: Does Low Expression of rmpA Contribute to the Absence of Hypervirulence?

Abstract

Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) has been increasingly reported and is now recognized as a significant threat to public health; however, characterization of MDR-hvKP has not been systematically investigated. In the present study, 124 of 428 (28.92%) K. pneumoniae clinical isolates collected from January 2010 to December 2016 were identified with aerobactin and defined as hvKP; these included 79 (48.77%) non-MDR-KP, 35 (15.63%) extended spectrum β-lactamase-producing K. pneumoniae (ESBL-KP), and 10 (23.81%) carbapenem-resistant K. pneumoniae (CR-KP) isolates. The remaining 304 isolates that were not hypervirulent phenotypes were defined as classic K. pneumoniae (cKP). The antimicrobial resistance rate of cKP was significantly higher than that of the hvKP isolates in the non-MDR-KP group, but showed no significant differences in the ESBL-KP and CR-KP groups. The detection frequencies of K1 serotype, hypermucoviscosity, sequence type 23 (ST23), and two virulence genes—mucoviscosity-associated gene A (magA) and regulator of mucoid phenotype A (rmpA)—were significantly high in the hvKP than cKP isolates in all three groups (P < 0.05). Most of the hypervirulent ESBL-KP and CR-KP isolates were K non-typeable (28/45) and harbored at least one gene for virulence (36/45). The hypervirulent ESBL-KP isolates primarily carried blaSHV (25/35, 71.42%) genes, and the hypervirulent CR-KP isolates mainly carried blaNDM-1 (8/10, 80%) genes. Moreover, four hypervirulent ESBL-KP and two hypervirulent CR-KP isolates showed resistance to tigecycline. The transcriptional levels of rmpA in cKP were much lower than that in hvKP isolates in all three groups. Furthermore, overexpression of rmpA could partly restore the hypervirulent phenotype of the rmpA-low-expression cKP isolates. In conclusion, our data suggest that the K1 serotype, rmpA, magA, hypermucoviscosity, and ST23 were strongly associated with hvKP in non-MDR-KP, ESBL-KP, and CR-KP groups, and low rmpA expression levels contributed to the absence of hypervirulent phenotype.