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(ΔGT-1) and K7(ΔwcaJ) 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.
Highlights
As important nosocomial and community-acquired opportunistic pathogens, Klebsiella pneumoniae (K. pneumoniae) spp. cause various infections, such as pneumonia, liver abscess, urinary tract infections, and complicated bacteremia (Podschun and Ullmann, 1998)
Both O antigen and K antigen are involved in phage adsorption on K. pneumoniae (Thurow et al, 1975; Tomás et al, 1987), but which component serves as primary phage adsorption receptor is still inconclusive
Rough-type phage-resistant K. pneumoniae strains caused by the mutations of primary phage receptors are much more common than the smoothtype after co-incubation of phage and host strain (Cai et al, 2018)
Summary
As important nosocomial and community-acquired opportunistic pathogens, Klebsiella pneumoniae (K. pneumoniae) spp. cause various infections, such as pneumonia, liver abscess, urinary tract infections, and complicated bacteremia (Podschun and Ullmann, 1998). With mutation in LPS or CPS synthetic genes, O antigen or K antigen of phage-resistant strains is generally lost resulting phenotype with comparatively smaller colony and much lower phage adsorption efficiency than the parental wild type strains (Le et al, 2014; Li et al, 2018). Both O antigen and K antigen are involved in phage adsorption on K. pneumoniae (Thurow et al, 1975; Tomás et al, 1987), but which component serves as primary phage adsorption receptor is still inconclusive
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