Thioredoxin A Is Essential for Motility and Contributes to Host Infection of Listeria monocytogenes via Redox Interactions

Frontiers in Cellular and Infection Microbiology

Wang, Hang¹  Yang, Yongchun¹  Freitag, Nancy E.¹  Cheng, Changyong¹  Wang, Xiaodu¹  Dong, Zhimei³  Huang, Huarong³  Chen, Zhongwei³  Ma, Tiantian³  Jiang, Li³  Fang, Weihuan⁶  Han, Xiao⁶  Song, Houhui⁶  Sun, Jing⁶  Shao, Chunyan⁶ 

[1] China-Australian Joint Laboratory for Animal Health Big Data Analytics, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection and Internet Technology, College of Animal Science and Technology of Zhejiang A&Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, United States;F University, Lin'Institute of Developmental and Regenerative Biology, College of Biological and Environmental Science, Hangzhou Normal University, Zhejiang, China;Zhejiang University Institute of Preventive Veterinary Medicine and Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine, Hangzhou, China;an, China

关键词: Listeria monocytogenes;    Thioredoxins;    motility;    Host infection;    Redox interaction;   

DOI  :  10.3389/fcimb.2017.00287

学科分类：生物科学（综合）

来源: Frontiers

【 摘 要 】

Microbes employ the thioredoxin system to defend against oxidative stress and ensure correct disulfide bonding to maintain protein function. Listeria monocytogenes has been shown to encode a putative thioredoxin, TrxA, but its biological roles and underlying mechanisms remain unknown. Here, we showed that expression of L. monocytogenes TrxA is significantly induced in bacteria treated with the thiol-specific oxidizing agent, diamide. Deletion of trxA markedly compromised tolerance of the pathogen to diamide, and mainly impaired early stages of infection in human intestinal epithelial Caco-2 cells. In addition, most trxA mutant bacteria were not associated with polymerized actin, and the rare bacteria that were associated with polymerized actin displayed very short tails or clouds during infection. Deletion or constitutive overexpression of TrxA, which was regulated by SigH, severely attenuated the virulence of the pathogen. Transcriptome analysis of L. monocytogenes revealed over 270 genes that were differentially transcribed in the ΔtrxA mutant compared to the wild-type, especially for the virulence-associated genes plcA, mpl, hly, actA and plcB. Particularly, deletion of TrxA completely reduced LLO expression, and thereby lead to a thoroughly impaired hemolytic activity. Expression of these virulence factors are positively regulated by the master regulator PrfA that was found here to use TrxA to maintain its reduced forms for activation. Interestingly, the trxA deletion mutant completely lacked flagella and was non-motile. We further confirmed that this deficiency is attributable to TrxA in maintaining the reduced intracellular monomer status of MogR, the key regulator for flagellar formation, to ensure correct dimerization. In summary, we demonstrated for the first time that L. monocytogenes thioredoxin A as a vital cellular reductase is essential for maintaining a highly reducing environment in the bacterial cytosol, which provides a favorable condition for protein folding and activation, and therefore contributes to bacterial virulence and motility.

【 授权许可】

CC BY