title: Haemophilus parasuis encodes two functional cytolethal distending toxins: CdtC contains an atypical cholesterol recognition/interaction region.
abstract: Haemophilus parasuis is the causative agent of Glässer's disease of pigs, a disease associated with fibrinous polyserositis, polyarthritis and meningitis. We report here H. parasuis encodes two copies of cytolethal distending toxins (Cdts), which these two Cdts showed the uniform toxin activity in vitro. We demonstrate that three Cdt peptides can form an active tripartite holotoxin that exhibits maximum cellular toxicity, and CdtA and CdtB form a more active toxin than CdtB and CdtC. Moreover, the cellular toxicity is associated with the binding of Cdt subunits to cells. Further analysis indicates that CdtC subunit contains an atypical cholesterol recognition/interaction amino acid consensus (CRAC) region. The mutation of CRAC site resulted in decreased cell toxicity. Finally, western blot analysis show all the 15 H. parasuis reference strains and 109 clinical isolates expressed CdtB subunit, indicating that Cdt is a conservative putative virulence factor for H. parasuis. This is the first report of the molecular and cellular basis of Cdt host interactions in H. parasuis.
authors.affiliation: National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Hubei, People's Republic of China.
authors.forename: Mingguang
authors.initials: M
authors.lastname: Zhou
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.forename: Meilin
authors.initials: M
authors.lastname: Jin
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D003851:Deoxyribonucleases / Q000378:metabolism; D004789:Enzyme Activation; D044137:Haemophilus parasuis / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D010802:Phylogeny; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D001427:Bacterial Toxins; D021122:Protein Subunits; D037521:Virulence Factors; C067044:cytolethal distending toxin; D002784:Cholesterol; D003851:Deoxyribonucleases