title: EmaA, a potential virulence determinant of Aggregatibacter actinomycetemcomitans in infective endocarditis.
abstract: The gram-negative fastidious human oropharyngeal Aggregatibacter actinomycetemcomitans is implicated in the etiology of infective endocarditis. EmaA, an oligomeric coiled-coil adhesin homologous to YadA of Yersinia enterocolitica, was hypothesized to mediate the interaction of A. actinomycetemcomitans with collagen. Collagen, the most abundant protein in human bodies and the main component of extracellular matrix (ECM), predominates in the supporting tissue of cardiac valves. To extend our earlier studies using purified collagen to determine bacterial binding activities, we developed a tissue model using rabbit cardiac valves to investigate the interaction of A. actinomycetemcomitans with native collagen. The resected mitral valves, with or without removal of the endothelium, were incubated with equivalent numbers of the wild type and the isogenic emaA mutant defective in collagen binding. There was no difference in binding between the wild-type and the mutant strains when the endothelium remained intact. However, the emaA mutant was fivefold less effective than the wild-type strain in colonizing the exposed ECM. A 10-fold increase in the binding of the wild-type strain to ECM was observed compared with the intact endothelium. Similar observations were replicated in an in vivo endocarditis rabbit model; the emaA mutant was 10-fold less effective in the initial infection of the traumatized aortic valve. Colocalization studies indicated that A. actinomycetemcomitans bound to type I collagen. A. actinomycetemcomitans preferentially colonized the ECM and, together with the evidence that EmaA interacts with the native collagen, suggested that the adhesin is likely a potential virulence determinant of the bacterium in the initiation of infective endocarditis.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, 95 Carrigan Drive, Burlington, VT 05405, USA.
authors.forename: Gaoyan
authors.initials: G
authors.lastname: Tang
authors.forename: Todd
authors.initials: T
authors.lastname: Kitten
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Munro
authors.forename: George C
authors.initials: GC
authors.lastname: Wellman
authors.forename: Keith P
authors.initials: KP
authors.lastname: Mintz
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D016976:Aggregatibacter actinomycetemcomitans / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D008943:Mitral Valve / Q000382:microbiology / Q000648:ultrastructure; D011817:Rabbits; D014357:Trypsin; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D024042:Collagen Type I; D037521:Virulence Factors; D014357:Trypsin