AmpR Increases the Virulence of Carbapenem-Resistant Klebsiella pneumoniae by Regulating the Initial Step of Capsule Synthesis.

Autor: Zhang, Min, Zhang, Jinyong, Li, Jia, Wu, Xianglin, Xiao, Lihua, Liu, Xueyan, Yang, Xiyao, Yang, Liqi, Zou, Quanming, Huang, Wei
Předmět:
Zdroj: Infection & Drug Resistance; Oct2020, Vol. 13, p3431-3441, 11p
Abstrakt: Background: Non-hypermucoviscous carbapenem-resistant Klebsiella pneumoniae with enhanced virulence lacking hvKP-specific virulence factors is uncommon, and the virulence mechanisms of this organism are not understood. Methods: Following a retrospective study of carbapenem-resistant K. pneumoniae based on core genome multilocus sequence typing (cgMLST), isolates that caused high mortality were investigated with a genome-wide association study (GWAS), proteome analysis and an animal model. Results: The subclone of sequence type 11 (ST11) K. pneumoniae, which belongs to complex type 3176 (CT3176) and K-locus 47 (KL47), was highlighted due to the high mortality of infected patients. GWAS analysis showed that transcriptional regulatory gene ampR was associated with the CT3176 isolates. In a mouse model, the mortality, bacterial load and pathological changes of mice infected with ampR-carrying isolates were distinct from those infected with ampR-null isolates. The ampR gene that enhances the virulence of the non-hypermucoviscous KL47 strain was unable to enhance the virulence of hypermucoviscous KL1 strain. Proteome analysis showed that the expression of WcaJ in the ampR+ isolates was significantly higher than that in the ampR isolates. Quantification of capsular polysaccharide confirmed that more capsule polysaccharide was produced by ampR+ and ampR-complementary strains compared to ampR strains. It is suggested that the enhancement of the initial stage of capsule synthesis may be the cause of the enhanced virulence of these non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae isolates. Conclusion: Non-hypermucoviscous ST11 carbapenem-resistant K. pneumoniae with enhanced virulence warrants continued surveillance and investigation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index