Emergence of colistin-resistant hypervirulent <i>Klebsiella pneumoniae</i> (CoR-HvKp) in China

Abstract

Colistin is regarded as a last-resort agent to combat infections caused by multidrug-resistant (MDR) Gram-negative bacteria, especially carbapenem-resistant isolates. In recent years, reports of colistin-resistant <i>Klebsiella pneumoniae</i> (CoRKp) are increasing. However, the molecular mechanism and relevance of colistin resistance and virulence remain unclear. Fourteen CoRKp strains were retrospectively screened from 1884 clinical <i>K. pneumoniae</i> isolates during 2017-2018 in China. Six CoRKp strains belonging to ST11 were MDR strains. Plasmid-mediated mobile colistin-resistance genes had a low prevalence in CoRKp. Our results revealed that up-regulated expression of two-component systems, especially <i>phoPQ,</i> contributed more to colistin resistance. <i>mgrB</i> mutation was the most common molecular mechanism of colistin resistance, caused by either nonsense mutations or insertion sequences, which drove the overexpression of <i>phoPQ system</i>. This study also identified three novel point mutations in <i>pmrAB</i> system, in which D313N mutation in <i>pmrB</i> was proved to increase the MIC to colistin by 16-fold. In addition, 6 out of 14 CoRKP strains independently carried hypervirulence genes. All six strains showed medium-to-high virulence phenotype compared with NTUH-K2044 strain in mice intraperitoneal challenge models. We found that 4 strains were biofilm strong producers and transcriptome analysis revealed that three of them significantly up-regulated expression of type III fimbrial shaft gene <i>mrkA</i>. In conclusion, our result revealed the emergence of colistin-resistant and hypervirulent MDR <i>K. pneumoniae,</i> which is a noticeable superbug and could cause a severe challenge to public health.