Subtilisin-like protease-1 secreted through type IV secretion system contributes to high virulence of Streptococcus suis 2.
Streptococcus suis serotype 2 is an emerging zoonotic pathogen that triggered two outbreaks of streptococcal toxic shock syndrome (STSS) in China. Our previous research demonstrated that a type IV secretion system (T4SS) harbored in the 89K pathogenicity island contributes to the pathogenicity of S. suis 2. In the present study, a shotgun proteomics approach was employed to identify the effectors secreted by T4SS in S. suis 2, and surface-associated subtilisin-like protease-1 (SspA-1) was identified as a potential virulence effector. Western blot analysis and pull-down assay revealed that SspA-1 secretion depends on T4SS. Knockout mutations affecting sspA-1 attenuated S. suis 2 and impaired the pathogen's ability to trigger inflammatory response in mice. And purified SspA-1 induced the secretion of IL-6, TNF-α, and IL-12p70 in THP-1 cells directly. SspA-1 is the first T4SS virulence effector reported in Gram-positive bacteria. Overall, these findings allow us to gain further insights into the pathogenesis of T4SS and STSS.
Department of Microbiology, Third Military Medical University, Chongqing, China.
Supeng
S
Yin
Department of Microbiology, Third Military Medical University, Chongqing, China.
Ming
M
Li
Department of Microbiology, Third Military Medical University, Chongqing, China.
Xiancai
X
Rao
Department of Microbiology, Third Military Medical University, Chongqing, China.
Xinyue
X
Yao
Department of Microbiology, Third Military Medical University, Chongqing, China.
Qiu
Q
Zhong
Department of Microbiology, Third Military Medical University, Chongqing, China.
Min
M
Wang
Department of Microbiology, Third Military Medical University, Chongqing, China.
Jing
J
Wang
Institute of Burn Research, Southwest Hospital, Third Military Medical University, Chongqing, China.
Yizhi
Y
Peng
PLA Research Institute of Clinical Laboratory Medicine, Nanjing general hospital of Nanjing Military command, Nanjing 210002, China.
Jiaqi
J
Tang
Department of Microbiology, Third Military Medical University, Chongqing, China.
Fuquan
F
Hu
Department of Microbiology, Third Military Medical University, Chongqing, China.
Yan
Y
Zhao
D000818:Animals; D004196:Disease Outbreaks; D005260:Female; D055786:Gene Knockout Techniques; D044404:Genomic Islands / Q000235:genetics; D018664:Interleukin-12 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D012772:Shock, Septic / Q000382:microbiology*; D013290:Streptococcal Infections / Q000382:microbiology*; D017011:Streptococcus suis / Q000235:genetics / Q000472:pathogenicity*; D013381:Subtilisins / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000069319:Type IV Secretion Systems / Q000235:genetics* / Q000378:metabolism
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000069319:Type IV Secretion Systems; C577686:interleukin-6, mouse; D018664:Interleukin-12; D013381:Subtilisins