Ampr increases the virulence of carbapenem-resistant klebsiella pneumoniae by regulating the initial step of capsule synthesis

Zhang，Min1; Zhang，Jinyong2; Li，Jia3; Wu，Xianglin4; Xiao，Lihua4; Liu，Xueyan5; Yang，Xiyao6; Yang，Liqi7; Zou，Quanming2; Huang，Wei1

2020

10.2147/IDR.S269275

Infection and Drug Resistance   影响因子和分区

1178-6973

1178-6973

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 hypermu-coviscous 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 enhance-ment 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.

Capsule synthesis Carbapenem-resistant Klebsiella pneumonia Virulence

SCI

英语

第一

International Collaborative Research Fund[GJHZ20180413181716797] ; Free Inquiry Fund of Shenzhen Science and Technology Innovation Commission[JCYJ20180305163929948]

Infectious Diseases ; Pharmacology & Pharmacy

Infectious Diseases ; Pharmacology & Pharmacy

WOS:000576690100002

DOVE MEDICAL PRESS LTD

2-s2.0-85092128324

Scopus

1.Bacteriology & Antibacterial Resistance Surveillance Laboratory,Shenzhen Institute of Respiratory Diseases,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,518020,China
2.National Engineering Research Center of Immunological Products,Department of Microbiology and Biochemical Pharmacy,College of Pharmacy,Army Medical University,Chongqing,China
3.Department of Infection Control,Bengbu Third People’s Hospital,Bengbu,China
4.Department of Laboratory Medicine,University of Chinese Academy Sciences Shenzhen Hospital,Shenzhen,China
5.Intensive Care Unit,Shenzhen People’s Hospital (The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,518020,China
6.Department of Infection Control,Second Affiliated Hospital of Anhui Medical University,Hefei,China
7.Department of Infection Control,Fourth Affiliated Hospital of Anhui Medical University,Hefei,China

Zhang，Min,Zhang，Jinyong,Li，Jia,et al. Ampr increases the virulence of carbapenem-resistant klebsiella pneumoniae by regulating the initial step of capsule synthesis[J]. Infection and Drug Resistance,2020,13:3431-3441.

Zhang，Min.,Zhang，Jinyong.,Li，Jia.,Wu，Xianglin.,Xiao，Lihua.,...&Huang，Wei.(2020).Ampr increases the virulence of carbapenem-resistant klebsiella pneumoniae by regulating the initial step of capsule synthesis.Infection and Drug Resistance,13,3431-3441.

Zhang，Min,et al."Ampr increases the virulence of carbapenem-resistant klebsiella pneumoniae by regulating the initial step of capsule synthesis".Infection and Drug Resistance 13(2020):3431-3441.