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

Abstract

Multidrug-resistant hypervirulent <i>Klebsiella pneumoniae</i> (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%) <i>K. pneumoniae</i> clinical isolates collected from January 2010 to December 2016 were identified with aerobactin and defined as hvKP; these included 94 non-MDR-KP, 20 extended-spectrum β-lactamase-producing <i>K. pneumoniae</i> (ESBL-KP), and 10 carbapenem-resistant <i>K. pneumoniae</i> (CR-KP) isolates. The remaining 304 isolates without presence of virulence factor aerobactin were defined as classic <i>K. pneumoniae</i> (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 capsular serotype K1 (<i>magA</i>), hypermucoviscosity, sequence type 23 (ST23), and the virulence gene <i>rmpA</i> were significantly higher in the hvKP than cKP isolates in all three groups (<i>P</i> < 0.05). Most of the hypervirulent ESBL-KP and CR-KP isolates were K non-typeable (16/30) and harbored at least one gene for virulence (26/30). The hypervirulent ESBL-KP isolates primarily carried <i>bla</i> _<i>CTX-M</i> (12/20, 60%) genes, and the hypervirulent CR-KP isolates mainly carried <i>bla</i> _<i>NDM-</i> ₁ (8/10, 80%) genes. Moreover, three hypervirulent ESBL-KP and two hypervirulent CR-KP isolates showed resistance to tigecycline but were sensitive to colistin. The transcriptional levels of <i>rmpA</i> in cKP were much lower than that in hvKP isolates in all three groups. Furthermore, overexpression of <i>rmpA</i> in the <i>rmpA</i>-low-expression cKP isolates could enhance bacterial virulence in the mouse infection experiment. In conclusion, our data suggest that the capsular serotype K1 (<i>magA</i>), <i>rmpA</i>, hypermucoviscosity, and ST23 were strongly associated with hvKP in non-MDR-KP, ESBL-KP, and CR-KP groups, and low <i>rmpA</i> expression levels contributed to the absence of hypervirulent phenotype.