title: Streptococcus mutans autolysin AtlA is a fibronectin-binding protein and contributes to bacterial survival in the bloodstream and virulence for infective endocarditis.
abstract: Streptococcus mutans, a commensal of the human oral cavity, can survive in the bloodstream and cause infective endocarditis (IE). However, the virulence factors associated with this manifestation of disease are not known. Here, we demonstrate that AtlA, an autolysin of S. mutans is a newly identified fibronectin (Fn) binding protein and contributes to bacterial resistance to phagocytosis and survival in the bloodstream. Interestingly, prior exposure to plasma at low concentrations was sufficient to enhance bacterial survival in the circulation. Calcium ions at physiological plasma concentrations induced maturation of AtlA from the 104-90 kDa isoform resulting in increased Fn binding and resistance to phagocytosis. An isogenic mutant strain defective in AtlA expression exhibited reduced survival and virulence when tested in a rat model of IE compared with the wild-type and complemented strains. The data presented suggest that plasma components utilized by S. mutans enhanced survival in the circulation and AtlA is a virulence factor associated with infective endocarditis.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, No. 1, Jen Ai Road Section 1, Taipei, 10051, Taiwan.
authors.forename: Chiau-Jing
authors.initials: CJ
authors.lastname: Jung
authors.forename: Quan-Hau
authors.initials: QH
authors.lastname: Zheng
authors.forename: Ya-Hsiung
authors.initials: YH
authors.lastname: Shieh
authors.forename: Chi-Shuan
authors.initials: CS
authors.lastname: Lin
authors.forename: Jean-San
authors.initials: JS
authors.lastname: Chia
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001769:Blood / Q000382:microbiology*; D001770:Blood Bactericidal Activity; D015169:Colony Count, Microbial; D004696:Endocarditis / Q000382:microbiology*; D017353:Gene Deletion; D006801:Humans; D050296:Microbial Viability; D008954:Models, Biological; D008970:Molecular Weight; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010587:Phagocytosis / Q000276:immunology; D011499:Protein Processing, Post-Translational; D051381:Rats; D017208:Rats, Wistar; D013295:Streptococcus mutans / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; C078635:fibronectin-binding proteins, bacterial; D009238:N-Acetylmuramoyl-L-alanine Amidase