title: The AgI/II family adhesin AspA is required for respiratory infection by Streptococcus pyogenes.
abstract: Streptococcus pyogenes (GAS) is a human pathogen that causes pharyngitis and invasive diseases such as toxic shock syndrome and sepsis. The upper respiratory tract is the primary reservoir from which GAS can infect new hosts and cause disease. The factors involved in colonisation are incompletely known however. Previous evidence in oral streptococci has shown that the AgI/II family proteins are involved. We hypothesized that the AspA member of this family might be involved in GAS colonization. We describe a novel mouse model of GAS colonization of the nasopharynx and lower respiratory tract to elucidate these interactions. We used two clinical M serotypes expressing AspA, and their aspA gene deletant isogenic mutants in experiments using adherence assays to respiratory epithelium, macrophage phagocytosis and neutrophil killing assays and in vivo models of respiratory tract colonisation and infection. We demonstrated the requirement for AspA in colonization of the respiratory tract. AspA mutants were cleared from the respiratory tract and were deficient in adherence to epithelial cells, and susceptible to phagocytosis. Expression of AspA in the surrogate host Lactococcus lactis protected bacteria from phagocytosis. Our results suggest that AspA has an essential role in respiratory infection, and may function as a novel anti-phagocytic factor.
authors: Department of Infection, Immunity and Inflammation, University of Leicester, Leicester, United Kingdom.
authors: Linda
authors: L
authors: Franklin
authors: Angela H
authors: AH
authors: Nobbs
authors: Laura
authors: L
authors: Bricio-Moreno
authors: Christopher J
authors: CJ
authors: Wright
authors: Sarah E
authors: SE
authors: Maddocks
authors: Jaspreet Singh
authors: JS
authors: Sahota
authors: Joe
authors: J
authors: Ralph
authors: Matthew
authors: M
authors: O'Connor
authors: Howard F
authors: HF
authors: Jenkinson
authors: Aras
authors: A
authors: Kadioglu
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics* / Q000276:immunology; D000818:Animals; D001422:Bacterial Adhesion; D002460:Cell Line; D005260:Female; D017353:Gene Deletion; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology; D010587:Phagocytosis; D012137:Respiratory System / Q000276:immunology / Q000382:microbiology*; D012141:Respiratory Tract Infections / Q000276:immunology / Q000382:microbiology*; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology*; D013297:Streptococcus pyogenes / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology
chemical_list: D018829:Adhesins, Bacterial
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