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- Title
Three Capsular Polysaccharide Synthesis-Related Glucosyltransferases, GT-1, GT-2 and WcaJ, Are Associated With Virulence and Phage Sensitivity of Klebsiella pneumoniae.
- Authors
Cai, Ruopeng; Wang, Gang; Le, Shuai; Wu, Mei; Cheng, Mengjun; Guo, Zhimin; Ji, Yalu; Xi, Hengyu; Zhao, Caijun; Wang, Xinwu; Xue, Yibing; Wang, Zijing; Zhang, Hao; Fu, Yunhe; Sun, Changjiang; Feng, Xin; Lei, Liancheng; Yang, Yongjun; ur Rahman, Sadeeq; Liu, Xiaoyun
- Abstract
Klebsiella pneumoniae (K. pneumoniae) spp. are important nosocomial and community-acquired opportunistic pathogens, which cause various infections. We observed that K. pneumoniae strain K7 abruptly mutates to rough-type phage-resistant phenotype upon treatment with phage GH-K3. In the present study, the rough-type phage-resistant mutant named K7RR showed much lower virulence than K7. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis indicated that WcaJ and two undefined glycosyltransferases (GTs)- named GT-1, GT-2- were found to be down-regulated drastically in K7RR as compared to K7 strain. GT-1 , GT-2 , and wcaJ are all located in the gene cluster of capsular polysaccharide (CPS). Upon deletion, even of single component, of GT-1 , GT-2 , and wcaJ resulted clearly in significant decline of CPS synthesis with concomitant development of GH-K3 resistance and decline of virulence of K. pneumoniae , indicating that all these three GTs are more likely involved in maintenance of phage sensitivity and bacterial virulence. Additionally, K7RR and GT-deficient strains were found sensitive to endocytosis of macrophages. Mitogen-activated protein kinase (MAPK) signaling pathway of macrophages was significantly activated by K7RR and GT-deficient strains comparing with that of K7. Interestingly, in the presence of macromolecular CPS residues (>250 KD), K7(Δ GT-1) and K7(Δ wcaJ) could still be bounded by GH-K3, though with a modest adsorption efficiency, and showed minor virulence, suggesting that the CPS residues accumulated upon deletion of GT-1 or wcaJ did retain phage binding sites as well maintain mild virulence. In brief, our study defines, for the first time, the potential roles of GT-1, GT-2, and WcaJ in K. pneumoniae in bacterial virulence and generation of rough-type mutation under the pressure of bacteriophage.
- Subjects
KLEBSIELLA pneumoniae; LIQUID chromatography-mass spectrometry; GLYCOSYLTRANSFERASES; MITOGEN-activated protein kinases; BACTERIOPHAGES
- Publication
Frontiers in Microbiology, 2019, pN.PAG
- ISSN
1664-302X
- Publication type
Article
- DOI
10.3389/fmicb.2019.01189