- Thioredoxin A of Streptococcus suis Serotype 2 Contributes to Virulence by Inhibiting the Expression of Pentraxin 3 to Promote Survival Within Macrophages
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Chijun Zhao , Xinglin Jia , Yanying Pan , Simeng Liao , Shuo Zhang , Chunxiao Ji , Guangwei Kuang , Xin Wu , Quan Liu , Yulong Tang , Lihua Fang
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J. Microbiol. 2023;61(4):433-448. Published online April 3, 2023
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DOI: https://doi.org/10.1007/s12275-023-00038-4
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 Abstract
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Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen that can infect humans in contact with infected pigs
or their byproducts. It can employ different types of genes to defend against oxidative stress and ensure its survival. The
thioredoxin (Trx) system is a key antioxidant system that contributes adversity adaptation and pathogenicity. SS2 has been
shown to encode putative thioredoxin genes, but the biological roles, coding sequence, and underlying mechanisms remains
uncharacterized. Here, we demonstrated that SSU05_0237-ORF, from a clinical SS2 strain, ZJ081101, encodes a protein
of 104 amino acids with a canonical CGPC active motif and an identity 70–85% similar to the thioredoxin A (TrxA) in
other microorganisms. Recombinant TrxA efficiently catalyzed the thiol-disulfide oxidoreduction of insulin. The deletion
of TrxA led to a significantly slow growth and markedly compromised tolerance of the pathogen to temperature stress,
as well as impaired adhesion ability to pig intestinal epithelial cells (IPEC-J2). However, it was not involved in H2O2
and
paraquat-induced oxidative stress. Compared with the wild-type strain, the ΔTrxA strain was more susceptible to killing by
macrophages through increasing NO production. Treatment with TrxA mutant strain also significantly attenuated cytotoxic
effects on RAW 264.7 cells by inhibiting inflammatory response and apoptosis. Knockdown of pentraxin 3 in RAW 264.7
cells was more vulnerable to phagocytic activity, and TrxA promoted SS2 survival in phagocytic cells depending on pentraxin
3 activity compared with the wild-type strain. Moreover, a co-inoculation experiment in mice revealed that TrxA mutant
strain is far more easily cleared from the body than the wild type strain in the period from 8–24 h, and exhibits significantly
attenuated oxidative stress and liver injury. In summary, we reveal the important role of TrxA in the pathogenesis of SS2.
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Citations
Citations to this article as recorded by  -
Pathogenicity and virulence of
Streptococcus suis
serotype 2: Emerging insights and persistent knowledge gaps
Lihua Fang, Yueru Yao, Jinmei Wu, Jie Ning
Virulence.2026;[Epub] CrossRef - Unraveling Streptococcus suis: Epidemiology, pathogenesis, and interventions of an emerging zoonosis
Miao Zhang, Yuanjie Zhao, Jinxiu Wang, Mengmeng Liu, Yun Zhang
hLife.2026;[Epub] CrossRef - Decadal advances and future prospects in subunit vaccine development against Streptococcus suis infection
Lihua Fang, Jie Ning
Frontiers in Immunology.2025;[Epub] CrossRef - Thioredoxin C of Streptococcus suis serotype 2 contributes to virulence by inducing antioxidative stress and inhibiting autophagy via the MSR1/PI3K-Akt-mTOR pathway in macrophages
Chunxiao Ji, Yanying Pan, Bocheng Liu, Jianying Liu, Chijun Zhao, Zhuyuan Nie, Simeng Liao, Guangwei Kuang, Xin Wu, Quan Liu, Jie Ning, Yulong Tang, Lihua Fang
Veterinary Microbiology.2024; 298: 110263. CrossRef - A Comprehensive Review on the Roles of Metals Mediating Insect–Microbial Pathogen Interactions
Subhanullah Khan, Minglin Lang
Metabolites.2023; 13(7): 839. CrossRef
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