title: The relationship of the lipoprotein SsaB, manganese and superoxide dismutase in Streptococcus sanguinis virulence for endocarditis.
abstract: Streptococcus sanguinis colonizes teeth and is an important cause of infective endocarditis. Our prior work showed that the lipoprotein SsaB is critical for S. sanguinis virulence for endocarditis and belongs to the LraI family of conserved metal transporters. In this study, we demonstrated that an ssaB mutant accumulates less manganese and iron than its parent. A mutant lacking the manganese-dependent superoxide dismutase, SodA, was significantly less virulent than wild-type in a rabbit model of endocarditis, but significantly more virulent than the ssaB mutant. Neither the ssaB nor the sodA mutation affected sensitivity to phagocytic killing or efficiency of heart valve colonization. Animal virulence results for all strains could be reproduced by growing bacteria in serum under physiological levels of O(2). SodA activity was reduced, but not eliminated in the ssaB mutant in serum and in rabbits. Growth of the ssaB mutant in serum was restored upon addition of Mn(2+) or removal of O(2). Antioxidant supplementation experiments suggested that superoxide and hydroxyl radicals were together responsible for the ssaB mutant's growth defect. We conclude that manganese accumulation mediated by the SsaB transport system imparts virulence by enabling cell growth in oxygen through SodA-dependent and independent mechanisms.
authors.affiliation: Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, VA, 23298, USA.
authors.forename: Katie E
authors.initials: KE
authors.lastname: Crump
authors.forename: Brian
authors.initials: B
authors.lastname: Bainbridge
authors.forename: Sarah
authors.initials: S
authors.lastname: Brusko
authors.forename: Lauren S
authors.initials: LS
authors.lastname: Turner
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Ge
authors.forename: Victoria
authors.initials: V
authors.lastname: Stone
authors.forename: Ping
authors.initials: P
authors.lastname: Xu
authors.forename: Todd
authors.initials: T
authors.lastname: Kitten
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004697:Endocarditis, Bacterial / Q000382:microbiology*; D055786:Gene Knockout Techniques; D007501:Iron / Q000378:metabolism; D008074:Lipoproteins / Q000172:deficiency / Q000378:metabolism*; D008345:Manganese / Q000378:metabolism*; D011817:Rabbits; D013291:Streptococcus / Q000378:metabolism / Q000472:pathogenicity*; D013482:Superoxide Dismutase / Q000378:metabolism*; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D008074:Lipoproteins; D037521:Virulence Factors; C067560:saliva-binding protein, Streptococcus sanguis 12; D008345:Manganese; D007501:Iron; C095500:SodA protein, Bacteria; D013482:Superoxide Dismutase
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