Superoxide dismutase of Streptococcus suis serotype 2 plays a role in anti-autophagic response by scavenging reactive oxygen species in infected macrophages

Fang, Lihua; Shen, Hongxia; Tang, Yulong; Fang, Weihuan

doi:10.1016/j.vetmic.2015.02.006

Cited by 25 publications

(23 citation statements)

References 30 publications

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“…Phagocytosis-associated respiratory burst would generate antimicrobial reactive oxygen species (ROS) including superoxide anion (

O_{2}^{• -}

), hydrogen peroxide (H 2 O 2 ), and hydroxyl radical ( • OH) (Forman and Torres, 2002; Fang et al, 2015; Zheng et al, 2016). We attempted an in vitro oxidative stress assay using non-lethal dose of hydrogen peroxide to mimic host-bacteria interaction in vivo to examine if such exposure would affect expression of virD4 itself and hence the release of secreted proteins.…”

Section: Discussionmentioning

confidence: 99%

Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis of Streptococcus suis Type 2

Jiang

Yang

Zhou

et al. 2016

Front. Cell. Infect. Microbiol.

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Streptococcus suis type 2 (SS2) is a zoonotic pathogen causing septic infection, meningitis and pneumonia in pigs and humans. SS2 may cause streptococcal toxic shock syndrome (STSS) probably due to excessive release of inflammatory cytokines. A previous study indicated that the virD4 gene in the putative type IV-like secretion system (T4SS) within the 89K pathogenicity island specific for recent epidemic strains contributed to the development of STSS. However, the functional basis of VirD4 in STSS remains unclear. Here we show that deletion of virD4 led to reduced virulence as shown by about 65% higher LD50, lower bacterial load in liver and brain, and lower level of expression of inflammatory cytokines in mice and cell lines than its parent strain. The ΔVirD4 mutant was more easily phagocytosed, suggesting its role as an anti-phagocytic factor. Oxidative stress that mimic bacterial exposure to respiratory burst of phagocytes upregulated expression of virD4. Proteomic analysis identified 10 secreted proteins of significant differences between the parent and mutant strains under oxidative stress, including PrsA, a peptidyl-prolyl isomerase. The SS2 PrsA expressed in E. coli caused a dose-dependent cell death and increased expression of proinflammatory IL-1β, IL-6 and TNF-α in murine macrophage cells. Our data provide novel insights into the contribution of the VirD4 factor to STSS pathogenesis, possibly via its anti-phagocytic activity, upregulation of its expression upon oxidative stress and its involvement in increased secretion of PrsA as a cell death inducer and proinflammatory effector.

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“…Phagocytosis-associated respiratory burst would generate antimicrobial reactive oxygen species (ROS) including superoxide anion (

O_{2}^{• -}

Section: Discussionmentioning

confidence: 99%

Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis of Streptococcus suis Type 2

Jiang

Yang

Zhou

et al. 2016

Front. Cell. Infect. Microbiol.

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“…Group B streptococcus (GBS) induces autophagy during infection of EC, but still resides primarily in single membrane-bound compartments, suggesting that GBS evades targeting to autophagosomes[41]. Streptococcus suis blocks xenophagy during infection of macrophages by secreting superoxide dismutase to scavenge cellular ROS[42]. Salmonella enterica serovar Typhimurium uses a type III secretion system (T3SS-1) to invade epithelial cells and form the Salmonella -containing vacuole (SCV).…”

Section: Xenophagy Beyond M Tuberculosis As Revealed By Cell Culturementioning

confidence: 99%

Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

Kimmey

Stallings

2016

Trends in Molecular Medicine

131

117

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Research in recent years has focused significantly on the role of selective macroautophagy in targeting intracellular pathogens for lysosomal degradation, a process termed xenophagy. In this review we evaluate the proposed roles for xenophagy in controlling bacterial infection, highlighting the concept that successful pathogens have evolved ways to subvert or exploit this defense, minimizing the actual effectiveness of xenophagy in innate immunity. Instead, studies in animal models have revealed that autophagy-associated proteins often function outside of xenophagy to influence bacterial pathogenesis. In light of current efforts to manipulate autophagy and the development of host-directed therapies to fight bacterial infections, we also discuss the implications stemming from the complicated relationship that exists between autophagy and bacterial pathogens.

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“…11 These included nox (SSUSC84_0648, encoding NADH oxidase), tpx (SSUSC84_1246, encoding thiol peroxidase), copA (SSUSC84_1247, encoding copper-transporting ATPase), and sodA (SSUSC84_1386, encoding superoxide dismutase). 11 Genes nox, tpx and sodA have been well studied and reported to be involved in oxidative stress responses and/or virulence in various streptococci and other bacteria, [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] while copA has been shown to be implicated in copper resistance. [30][31][32] Additionally, an undefined gene, 0350 (SSUSC84_0350, encoding a hypothetical protein) is potentially involved in oxidative stress and/or virulence, as it was downregulated 8.7-fold in DspxA1.…”

Section: Introductionmentioning

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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Superoxide dismutase of Streptococcus suis serotype 2 plays a role in anti-autophagic response by scavenging reactive oxygen species in infected macrophages

Cited by 25 publications

References 30 publications

Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis of Streptococcus suis Type 2

Roles of the Putative Type IV-like Secretion System Key Component VirD4 and PrsA in Pathogenesis of Streptococcus suis Type 2

Bacterial Pathogens versus Autophagy: Implications for Therapeutic Interventions

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

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