title: Structural basis of the novel S. pneumoniae virulence factor, GHIP, a glycosyl hydrolase 25 participating in host-cell invasion.
abstract: Pathogenic bacteria produce a wide variety of virulence factors that are considered to be potential antibiotic targets. In this study, we report the crystal structure of a novel S. pneumoniae virulence factor, GHIP, which is a streptococcus-specific glycosyl hydrolase. This novel structure exhibits an α/β-barrel fold that slightly differs from other characterized hydrolases. The GHIP active site, located at the negatively charged groove in the barrel, is very similar to the active site in known peptidoglycan hydrolases. Functionally, GHIP exhibited weak enzymatic activity to hydrolyze the PNP-(GlcNAc)5 peptidoglycan by the general acid/base catalytic mechanism. Animal experiments demonstrated a marked attenuation of S. pneumoniae-mediated virulence in mice infected by ΔGHIP-deficient strains, suggesting that GHIP functions as a novel S. pneumoniae virulence factor. Furthermore, GHIP participates in allowing S. pneumoniae to colonize the nasopharynx and invade host epithelial cells. Taken together, these findings suggest that GHIP can potentially serve as an antibiotic target to effectively treat streptococcus-mediated infection.
authors.affiliation: Department of Laboratory Medicine, Chongqing Medical University, Chongqing, People's Republic of China.
authors.forename: Siqiang
authors.initials: S
authors.lastname: Niu
authors.forename: Miao
authors.initials: M
authors.lastname: Luo
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.forename: Yangli
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xun
authors.initials: X
authors.lastname: Min
authors.forename: Xuefei
authors.initials: X
authors.lastname: Cai
authors.forename: Wenlu
authors.initials: W
authors.lastname: Zhang
authors.forename: Wenchu
authors.initials: W
authors.lastname: Xu
authors.forename: Defeng
authors.initials: D
authors.lastname: Li
authors.forename: Jingjin
authors.initials: J
authors.lastname: Ding
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Hu
authors.forename: Dacheng
authors.initials: D
authors.lastname: Wang
authors.forename: Ailong
authors.initials: A
authors.lastname: Huang
authors.forename: Yibin
authors.initials: Y
authors.lastname: Yin
authors.forename: Deqiang
authors.initials: D
authors.lastname: Wang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D005260:Female; D006801:Humans; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D011008:Pneumococcal Infections / Q000201:enzymology*; D013296:Streptococcus pneumoniae / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity*; D037521:Virulence Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D037521:Virulence Factors; C000592809:glycosyl hydrolase 25 relating to invasion protein, Streptococcus pneumoniae; D006867:Hydrolases