IADR Abstract Archives

LraI System and Manganese in Streptococcus sanguinis Virulence for Endocarditis

Streptococcus sanguinis is a normal inhabitant of the mouth and an important cause of infective endocarditis.  SsaB, a protein belonging to a family of orthologous metal-transport proteins termed Lipoprotein Receptor Antigen I (LraI), is critical for endocarditis virulence in S. sanguinis.  While LraI proteins have been shown to transport manganese and additional metals, the role of metal homeostasis in oxygen tolerance has yet to be elucidated for S. sanguinis.

Objective: The aim of this study was to determine the specific role of manganese in oxygen tolerance and virulence for endocarditis in Streptococcus sanguinis.

Method: Isogenic mutants lacking SsaB, the manganese-dependent superoxide dismutase, SodA, or both, in S. sanguinis were generated.  Using an in vivo rabbit model for endocarditis and in vitro growth assays, wild-type and mutant S. sanguinis virulence, metal composition, colonization, growth characteristics, SodA activity, and oxidative stress were assessed.      

Result:  The role of SsaB as a metal transporter was confirmed by reduction of cellular manganese and iron levels in the ssaB mutant.  In an animal model of endocarditis, all three mutants exhibited reduced virulence, with the double mutant exhibiting the greatest defect and the sodA mutant, the least.  This reduction of virulence was not due to diminished resistance to phagocytic killing or heart valve colonization in either single mutant.  Furthermore, the relative virulence of wild-type and mutant strains was reproduced by a growth assay employing only normal rabbit serum and physiological levels of oxygen.  Using these physiological conditions, SodA activity was decreased but not absent in the ssaB mutant.  Additionally, antioxidant studies suggested that increased damage by superoxide was necessary for the ssaB mutant’s reduced-growth phenotype, but not sufficient, with additional contributions by hydroxyl radicals likely.  

Conclusion: These studies indicate that SsaB-mediated manganese uptake enables virulence by providing resistance to oxidative stress through both SodA-dependent and independent mechanisms.

AADR/CADR Annual Meeting
2014 AADR/CADR Annual Meeting (Charlotte, North Carolina)
Charlotte, North Carolina
2014
811
Microbiology / Immunology
  • Crump, Katie  ( Virginia Commonwealth University, Richmond, VA, USA )
  • Bainbridge, Brian  ( University of Florida, Gainesville, Florida, Gainesville, FL, USA )
  • Brusko, Sarah  ( Virginia Commonwealth University, Richmond, VA, USA )
  • Turner, Lauren  ( Commonwealth of Virginia Division of Consolidated Laboratory Services, Richmond, VA, USA )
  • Ge, Xiuchun  ( Virginia Commonwealth University, Richmond, VA, USA )
  • Stone, Victoria  ( Virginia Commonwealth University, Richmond, VA, USA )
  • Xu, Ping  ( Virginia Commonwealth University, Richmond, VA, USA )
  • Kitten, Todd  ( Virginia Commonwealth University, Richmond, VA, USA )
    • Oral Session
    Streptococci
    03/21/2014