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

• Published in: Frontiers in cellular and infection microbiology 2017-06, Vol.7, p.287-287
• Main Authors: Cheng, Changyong, Dong, Zhimei, Han, Xiao, Wang, Hang, Jiang, Li, Sun, Jing, Yang, Yongchun, Ma, Tiantian, Shao, Chunyan, Wang, Xiaodu, Chen, Zhongwei, Fang, Weihuan, Freitag, Nancy E, Huang, Huarong, Song, Houhui
• Format: Article
• Language: English
• Subjects: Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Caco-2 Cells; Cytosol - metabolism; Flagella - genetics; Flagella - metabolism; Gene Expression Regulation, Bacterial; host infection; Humans; Listeria monocytogenes; Listeria monocytogenes - cytology; Listeria monocytogenes - genetics; Listeria monocytogenes - metabolism; Listeria monocytogenes - pathogenicity; Listeriosis - metabolism; Listeriosis - microbiology; Microbiology; motility; Oxidation-Reduction; redox interaction; thioredoxins; Thioredoxins - genetics; Thioredoxins - metabolism; Virulence
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2017.00287

Microbes employ the thioredoxin system to defend against oxidative stress and ensure correct disulfide bonding to maintain protein function. has been shown to encode a putative thioredoxin, TrxA, but its biological roles and underlying mechanisms remain unknown. Here, we showed that expression of TrxA is significantly induced in bacteria treated with the thiol-specific oxidizing agent, diamide. Deletion of 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 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 revealed over 270 genes that were differentially transcribed in the Δ mutant compared to the wild-type, especially for the virulence-associated genes , and . Particularly, deletion of TrxA completely reduced LLO expression, and thereby led 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 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 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.