Identification and characterization of the chromosomal yefM-yoeB toxin-antitoxin system of Streptococcus suis

Zheng, Chengkun; Xu, Jiali; Ren, Sujing; Li, Jinquan; Xia, Mengna; Chen, Huanchun; Bei, Weicheng

doi:10.1038/srep13125

Cited by 29 publications

(29 citation statements)

References 47 publications

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“…The mutant Δ sly was constructed in SC19 using the thermosensitive suicide plasmid pSET4s ( Takamatsu et al, 2001a ), as described previously ( Zhang et al, 2016 ). Its complementation strain SC19 Δ sly::sly was generated using the Escherichia coli–Streptococcus suis shuttle vector pSET2 ( Takamatsu et al, 2001b ), as described previously ( Zheng et al, 2015 ). SC19 and Δ sly were grown in tryptic soy broth (TSB) or plated on tryptic soy agar (TSA) (Difco Laboratories, Detroit, MI, United States) with 10% newborn bovine serum added (Sijiqing Biological Engineering Materials Co., Ltd., Hangzhou, China) at 37°C.…”

Section: Methodsmentioning

confidence: 99%

Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin

et al. 2018

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Streptococcus suis serotype 2 is a serious zoonotic pathogen and has attracted worldwide attention since the first human case was reported in Denmark in 1968. Some virulence factors have been reported to be involved in the pathogenesis of the infection caused by Streptococcus suis serotype 2, and then novel strategies to identify some anti-virulence compounds which can effectively inhibit the pathogenic bacterial infection have recently been reported. Suilysin is an essential virulence factor for Streptococcus suis serotype 2 since it creates pores in the target cells membranes, which aids bacterial colonization. The important role of suilysin in the virulence of Streptococcus suis serotype 2 renders it an ideal target for designing novel anti-virulence therapeutics. We find that fisetin, as a natural flavonoid, is a potent antagonist against suilysin-mediated hemolysis. The aim of this study is to evaluate the effect of fisetin on the hemolytic activity of suilysin from Streptococcus suis serotype 2. Fisetin is found to significantly inhibit the hemolytic activity of suilysin. Within the range of effective concentrations, fisetin does not influence the growth of Streptococcus suis serotype 2 and the expression of suilysin protein. In vitro, fisetin effectively inhibits the death of macrophages (J774A.1 and RAW264.7) infected with Streptococcus suis serotype 2 by weakening intracellular bacterial multiplication. Animal model experiment shows that fisetin effectively improves the survival rate of animals infected with Streptococcus suis serotype 2. Our findings suggest that fisetin could be used as an antitoxin against suilysin and be developed into a promising therapeutic candidate for treating Streptococcus suis serotype 2 infection.

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Section: Methodsmentioning

confidence: 99%

Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin

et al. 2018

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“…Ectopic overexpression of YoeB was shown to be toxic to E. coli but YefM counteracted this toxicity (Grady and Hayes, 2003 ). Since then, the yefM-yoeB TA system has been found in diverse bacterial species including S. pneumoniae (Nieto et al, 2007 ; Chan et al, 2011 ), Streptococcus suis (Zheng et al, 2015 ), M. tuberculosis (Kumar et al, 2008 ), Staphylococcus aureus (Yoshizumi et al, 2009 ), Staphylococcus equorum (Nolle et al, 2013 ), Lactobacillus rhamnosus (Krügel et al, 2015 ), and Streptomyces (Sevillano et al, 2012 ).…”

Section: The Hybrid Yefm-yoeb Ta System: Further Complexities In Ta Rmentioning

confidence: 99%

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems

Chan

Espinosa

Yeo

2016

Front. Mol. Biosci.

123

121

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In their initial stages of discovery, prokaryotic toxin-antitoxin (TA) systems were confined to bacterial plasmids where they function to mediate the maintenance and stability of usually low- to medium-copy number plasmids through the post-segregational killing of any plasmid-free daughter cells that developed. Their eventual discovery as nearly ubiquitous and repetitive elements in bacterial chromosomes led to a wealth of knowledge and scientific debate as to their diversity and functionality in the prokaryotic lifestyle. Currently categorized into six different types designated types I–VI, type II TA systems are the best characterized. These generally comprised of two genes encoding a proteic toxin and its corresponding proteic antitoxin, respectively. Under normal growth conditions, the stable toxin is prevented from exerting its lethal effect through tight binding with the less stable antitoxin partner, forming a non-lethal TA protein complex. Besides binding with its cognate toxin, the antitoxin also plays a role in regulating the expression of the type II TA operon by binding to the operator site, thereby repressing transcription from the TA promoter. In most cases, full repression is observed in the presence of the TA complex as binding of the toxin enhances the DNA binding capability of the antitoxin. TA systems have been implicated in a gamut of prokaryotic cellular functions such as being mediators of programmed cell death as well as persistence or dormancy, biofilm formation, as defensive weapons against bacteriophage infections and as virulence factors in pathogenic bacteria. It is thus apparent that these antitoxins, as DNA-binding proteins, play an essential role in modulating the prokaryotic lifestyle whilst at the same time preventing the lethal action of the toxins under normal growth conditions, i.e., keeping the proverbial wolves at bay. In this review, we will cover the diversity and characteristics of various type II TA antitoxins. We shall also look into some interesting deviations from the canonical type II TA systems such as tripartite TA systems where the regulatory role is played by a third party protein and not the antitoxin, and a unique TA system encoding a single protein with both toxin as well as antitoxin domains.

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“…11 The complementation strain CDnox was generated using E. coli-S. suis shuttle vector pSET2, 45 as previously described. 46 The mutants (D0350, Dnox, Dtpx and DcopA) and the complementation strain CDnox were verified by PCR ( Fig. S4A), RT-PCR analysis (Fig.…”

Section: Construction Of Mutant Strains and Functional Complementatiomentioning

confidence: 99%

Contribution of NADH oxidase to oxidative stress tolerance and virulence ofStreptococcus suisserotype 2

Zheng

Ren

et al. 2016

Virulence

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Streptococcus suis is a major swine and zoonotic pathogen that causes severe infections. Previously, we identified 2 Spx regulators in S. suis, and demonstrated that SpxA1 affects oxidative stress tolerance and virulence. However, the mechanism behind SpxA1 function remains unclear. In this study, we targeted 4 genes that were expressed at significantly reduced levels in the spxA1 mutant, to determine their specific roles in adaptation to oxidative stress and virulence potential. The Δnox strain exhibited impaired growth under oxidative stress conditions, suggesting that NADH oxidase is involved in oxidative stress tolerance. Using murine and pig infection models, we demonstrate for the first time that NADH oxidase is required for virulence in S. suis 2. Furthermore, the enzymatic activity of NADH oxidase has a key role in oxidative stress tolerance and a secondary role in virulence. Collectively, our findings reveal that NADH oxidase plays an important part in SpxA1 function and provide a new insight into the pathogenesis of S. suis 2.

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Identification and characterization of the chromosomal yefM-yoeB toxin-antitoxin system of Streptococcus suis

Cited by 29 publications

References 47 publications

Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin

Fisetin Lowers Streptococcus suis serotype 2 Pathogenicity in Mice by Inhibiting the Hemolytic Activity of Suilysin

Keeping the Wolves at Bay: Antitoxins of Prokaryotic Type II Toxin-Antitoxin Systems

Contribution of NADH oxidase to oxidative stress tolerance and virulence ofStreptococcus suisserotype 2

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