title: Impact of the glpQ2 gene on virulence in a Streptococcus pneumoniae serotype 19A sequence type 320 strain.
abstract: Glycerophosphodiester phosphodiesterase (GlpQ) metabolizes glycerophosphorylcholine from the lung epithelium to produce free choline, which is transformed into phosphorylcholine and presented on the surfaces of many respiratory pathogens. Two orthologs of glpQ genes are found in Streptococcus pneumoniae: glpQ, with a membrane motif, is widespread in pneumococci, whereas glpQ2, which shares high similarity with glpQ in Haemophilus influenzae and Mycoplasma pneumoniae, is present only in S. pneumoniae serotype 3, 6B, 19A, and 19F strains. Recently, serotype 19A has emerged as an epidemiological etiology associated with invasive pneumococcal diseases. Thus, we investigated the pathophysiological role of glpQ2 in a serotype 19A sequence type 320 (19AST320) strain, which was the prevalent sequence type in 19A associated with severe pneumonia and invasive pneumococcal disease in pediatric patients. Mutations in glpQ2 reduced phosphorylcholine expression and the anchorage of choline-binding proteins to the pneumococcal surface during the exponential phase, where the mutants exhibited reduced autolysis and lower natural transformation abilities than the parent strain. The deletion of glpQ2 also decreased the adherence and cytotoxicity to human lung epithelial cell lines, whereas these functions were indistinguishable from those of the wild type in complementation strains. In a murine respiratory tract infection model, glpQ2 was important for nasopharynx and lung colonization. Furthermore, infection with a glpQ2 mutant decreased the severity of pneumonia compared with the parent strain, and glpQ2 gene complementation restored the inflammation level. Therefore, glpQ2 enhances surface phosphorylcholine expression in S. pneumoniae 19AST320 during the exponential phase, which contributes to the severity of pneumonia by promoting adherence and host cell cytotoxicity.
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China ypchuang@ndmctsgh.edu.tw ychsieh@cgmh.org.tw.
authors.forename: Yi-Ping
authors.initials: YP
authors.lastname: Chuang
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Zih-Rong
authors.initials: ZR
authors.lastname: Peng
authors.affiliation: Research Center of Bacterial Pathogenesis, Chang Gung University, Taoyuan, Taiwan, Republic of China.
authors.forename: Shun-Fu
authors.initials: SF
authors.lastname: Tseng
authors.affiliation: Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
authors.forename: Yu-Chun
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.affiliation: Department of Pediatrics, Chang Gung Children's Hospital, Chang Gung Memorial Hospital, Chang Gung University, College of Medicine, Taoyuan, Taiwan, Republic of China ypchuang@ndmctsgh.edu.tw ychsieh@cgmh.org.tw.
authors.forename: Yu-Chia
authors.initials: YC
authors.lastname: Hsieh
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001329:Autolysis / Q000235:genetics; D001422:Bacterial Adhesion / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics*; D002460:Cell Line; D004847:Epithelial Cells / Q000378:metabolism / Q000382:microbiology; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology; D051379:Mice; D008807:Mice, Inbred BALB C; D010727:Phosphoric Diester Hydrolases / Q000235:genetics*; D010767:Phosphorylcholine / Q000378:metabolism; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016415:Sequence Alignment; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D001426:Bacterial Proteins; D010767:Phosphorylcholine; D010727:Phosphoric Diester Hydrolases; C087921:glpQ protein, Bacteria