| Title | 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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| Author | Chijun Zhao1, Xinglin Jia1, Yanying Pan1, Simeng Liao2, Shuo Zhang2,3, Chunxiao Ji1, Guangwei Kuang2, Xin Wu2, Quan Liu4, Yulong Tang2,5*, and Lihua Fang4* |
| Address | 1College of Veterinary Medicine, Hunan Agricultural University, Changsha 410125, China, 2Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha 410125, China, 3South Southwest Agriculture and Animal Husbandry Group, Ltd, Kunming 650217, China, 4School of Life Science and Engineering, Foshan University, Foshan 528225, Guangdong, China, 5Anhui Province Key Laboratory of Livestock and Poultry Product Safety Engineering, Hefei 230001, China |
| Bibliography | Journal of Microbiology, 61(4),433-448, 2023, |
| DOI | 10.1007/s12275-023-00038-4 |
| Key Words | Streptococcus suis serotype 2 · Thioredoxin system · Anti-phagocytosis · Oxidative stress |
| Abstract | 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. |