Infection and Drug Resistance (Oct 2020)
AmpR Increases the Virulence of Carbapenem-Resistant Klebsiella pneumoniae by Regulating the Initial Step of Capsule Synthesis
Abstract
Min Zhang,1,* Jinyong Zhang,2,* Jia Li,3 Xianglin Wu,4 Lihua Xiao,4 Xueyan Liu,5 Xiyao Yang,6 Liqi Yang,7 Quanming Zou,2 Wei Huang1 1Bacteriology & 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, Guangdong 518020, People’s Republic of China; 2National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing, People’s Republic of China; 3Department of Infection Control,Bengbu Third People’s Hospital, Bengbu, Anhui, People’s Republic of China; 4Department of Laboratory Medicine, University of Chinese Academy Sciences Shenzhen Hospital, Shenzhen, Guangdong, People’s Republic of China; 5Intensive Care Unit, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong 518020, People’s Republic of China; 6Department of Infection Control, Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 7Department of Infection Control, Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei HuangBacteriology & 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 Guangdong 518020, People’s Republic of ChinaTel +86 07522942513Fax +86 07522942514Email [email protected] ZouNational Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Army Medical University, Chongqing 400038, People’s Republic of ChinaTel/ Fax +86 02368752316Email [email protected]: 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.Keywords: Klebsiella pneumonia, virulence, carbapenem-resistant, capsule synthesis
