Streptococcus suis adenosine synthase functions as an effector in evasion of PMN-mediated innate immunit.
Streptococcus suis serotype 2 (S. suis 2) is a highly invasive pathogen in pigs and humans that can cause severe systemic infection. Sepsis and meningitis are the most common clinical manifestations of S. suis 2 infection. However, the mechanisms of S. suis 2 surviving in human blood remains unclear, so to identify novel virulence factors in evasion of polymorphonuclear leukocyte (PMN)-mediated innate immunity play important roles in developing therapies against S. suis 2 infection. Here, we found that S. suis 2 can escape phagocytic clearance by adenosine synthesis in blood. Through bioinformatics-based analyses we identified a cell wall-anchored protein harbors a 5′-nucleotidase signature sequence and evidence strongly indicated that it can convert adenosine monophosphate (AMP) to adenosine. It was designated as Ssads (the adenosine synthase of S. suis 2). Furthermore, we found that Ssads could impair PMN's defense against S. suis 2 with decreasing of oxidative activity and degranulation of PMNs in human blood via A₂a receptors. Additionally, this enzyme-deﬁcient mutant was found to have diminished virulence in the piglet infection model. Taken together, these results indicate that Ssads play an important role in S. suis 2 escaping human innate immunity in the context of inhibiting PMN's activity by synthesis of adenosine.
Peng
P
Liu
Yaya
Y
Pian
Xueqin
X
Li
Renfeng
R
Liu
Wenlong
W
Xie
Chunmao
C
Zhang
Yuling
Y
Zheng
Yongqiang
Y
Jiang
Yuan
Y
Yuan
D000241:Adenosine / Q000096:biosynthesis*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D007113:Immunity, Innate; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology*; D010587:Phagocytosis; D017011:Streptococcus suis / Q000201:enzymology* / Q000276:immunology*; D013552:Swine; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
D001426:Bacterial Proteins; D037521:Virulence Factors; D000241:Adenosine