The Involvement Of SntA Protein In Pathogenesis Of Streptococcus Suis Serotype 2

The Gram-positive bacterium Streptococcus suis serotype 2(S.suis,SS2)becomes a very important emerging zoonotic pathogen in the world in recent years,especially in SoutheastAsia.Two large outbreaks of human infections in China were reported in 1998 and 2005.The most clinical presentations of these outbreaks were characterized as Streptococcal toxic shock-like syndrome(STSLS),including septicemia with septic shock and meningitis.During the infection,SS2 colonize the host,breach epithelial barriers,reach and survive in the bloodstream,invade different organs,and cause exaggerated inflammation.Many virulence factors have been shown to play specific roles in the pathogenesis of SS2 infection.However,the molecular mechanism of STSLS remains poorly understood.Many cell surface proteins are involved in the pathogenesis of bacterial pathogens.Our previous studies demonstrate that the cell surface protein SntA of SS2 was upregulated either under iron-restricted culture conditions or during infection of pigs,suggesting that it may involve in iron acquisition of SS2.The SntA protein is also reported to be absent from the 2D-PAGE profiles of sortase A gene deletion mutants of its RGD motif.In this study,SntA is identified as a novel heme-containing protein,which could interact with host antioxidant protein AOP2.The interaction could promote the oxidation of hemoglobin,resulting in more methemoglobin release into blood and tissues(methemoglobinemia).Compared to the isogenic mutant of sntA,the wild type strain induced arthritis,endocarditis,stronger subdural hemorrhage,microglia nodules and bacteria-like aggregate beneath the dura in intravenously infected pigs.The mutant strain displayed reduced colonization,tissue lesions and inflammation.This interaction may provide an explanation for the blood disorders and exaggerated inflammation caused by SS2 infection.Thus,the SntA is a novel virulence factor contributing to the in vivo survival and pathogenesis of SS2,especially the blood disorders and exaggerated inflammation caused by SS2 infection.This is the first report that a streptococcal heme-containing protein could induce methemoglobinemia and inflammation through interacting with AOP2.The characterization of this process provides new insights into bacterial cell wall function and pathogen-host interactions.