Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans

Hoeven, Ransome van der; McCallum, Katie C.; Cruz, Melissa R.; Garsin, Danielle A.

doi:10.1371/journal.ppat.1002453

Cited by 193 publications

(176 citation statements)

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“…Hoeven et al . (2011) have shown that ROS released from Ce‐Duox1/BLI‐3 can activate SKN‐1 activity via p38 MAPK signaling, with NSY‐1 and SEK‐1 both able to regulate the p38 MAPK ortholog PMK‐1. In response to oxidative stress, PMK‐1 phosphorylates SKN‐1, which then translocates to the nuclei of intestinal cells and induces the transcription of phase 2 detoxification genes (Inoue et al ., 2005).…”

Section: Discussionmentioning

confidence: 99%

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

et al. 2015

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SummaryLactic‐acid bacteria are widely recognized beneficial host associated groups of the microbiota of humans and animals. Some lactic‐acid bacteria have the ability to extend the lifespan of the model animals. The mechanisms behind the probiotic effects of bacteria are not entirely understood. Recently, we reported the benefit effects of Lactobacillus gasseri SBT2055 (LG2055) on animal and human health, such as preventing influenza A virus, and augmentation of IgA production. Therefore, it was preconceived that LG2055 has the beneficial effects on longevity and/or aging. We examined the effects of LG2055 on lifespan and aging of Caenorhabditis elegans and analyzed the mechanism of prolongevity. Our results demonstrated that LG2055 has the beneficial effects on longevity and anti‐aging of C. elegans. Feeding with LG2055 upregulated the expression of the skn‐1 gene and the target genes of SKN‐1, encoding the antioxidant proteins enhancing antioxidant defense responses. We found that feeding with LG2055 directly activated SKN‐1 activity via p38 MAPK pathway signaling. The oxidative stress response is elicited by mitochondrial dysfunction in aging, and we examined the influence of LG2055 feeding on the membrane potential of mitochondria. Here, the amounts of mitochondria were significantly increased by LG2055 feeding in comparison with the control. Our result suggests that feeding with LG2055 is effective to the extend lifespan in C. elegans by a strengthening of the resistance to oxidative stress and by stimulating the innate immune response signaling including p38MAPK signaling pathway and others.

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Section: Discussionmentioning

confidence: 99%

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

et al. 2015

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“…To investigate colonization during coinfection of the intestine, an adaptation of a previously used methodology was employed (41). After the nematodes were infected as described above and allowed to incubate for 4 or 7 days, they were washed with 2 ml of sterile M9W and collected by centrifugation at 1,000 rpm four times.…”

Section: Methodsmentioning

confidence: 99%

Enterococcus faecalis Inhibits Hyphal Morphogenesis and Virulence of Candida albicans

et al. 2013

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The Gram-positive bacterium Enterococcus faecalis and the fungus Candida albicans are both found as commensals in many of the same niches of the human body, such as the oral cavity and gastrointestinal (GI) tract. However, both are opportunistic pathogens and have frequently been found to be coconstituents of polymicrobial infections. Despite these features in common, there has been little investigation into whether these microbes affect one another in a biologically significant manner. Using a Caenorhabditis elegans model of polymicrobial infection, we discovered that E. faecalis and C. albicans negatively impact each other's virulence. Much of the negative effect of E. faecalis on C. albicans was due to the inhibition of C. albicans hyphal morphogenesis, a developmental program crucial to C. albicans pathogenicity. We discovered that the inhibition was partially dependent on the Fsr quorum-sensing system, a major regulator of virulence in E. faecalis. Specifically, two proteases regulated by Fsr, GelE and SerE, were partially required. Further characterization of the inhibitory signal revealed that it is secreted into the supernatant, is heat resistant, and is between 3 and 10 kDa. The substance was also shown to inhibit C. albicans filamentation in the context of an in vitro biofilm. Finally, a screen of an E. faecalis transposon mutant library identified other genes required for suppression of C. albicans hyphal formation. Overall, we demonstrate a biologically relevant interaction between two clinically important microbes that could affect treatment strategies as well as impact our understanding of interkingdom signaling and sensing in the human-associated microbiome.

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“…Exposure to RNAi, survival assays, and longevity assays were performed as previously described (Garsin et al , 2003Kim et al 2002;van der Hoeven et al 2011). Briefly, for E. faecalis survival assays, E. faecalis grown in brain heart infusion (BHI) medium for 5 hr was seeded (10 ml) onto BHI plates (gentamycin 50 mg/ml) and incubated at 37°for 24 hr, whereas for P. aeruginosa survival assays, P. aeruginosa was cultured in Luria broth (LB) overnight at 37°, seeded (10 ml) onto slow-killing plates, and incubated first for 24 hr at 37°and then for the duration of 516 G. R. Tiller and D. A. Garsin the experiment at 25°.…”

Section: Survival and Longevity Assaysmentioning

confidence: 99%

The SKPO-1 Peroxidase Functions in the Hypodermis to ProtectCaenorhabditis elegansFrom Bacterial Infection

Tiller

Garsin

2014

Genetics

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In recent years, the synergistic relationship between NADPH oxidase (NOX)/dual oxidase (DUOX) enzymes and peroxidases has received increased attention. Peroxidases utilize NOX/DUOX-generated H 2 O 2 for a myriad of functions including, but not limited to, thyroid hormone biosynthesis, cross-linking extracellular matrices (ECM), and immune defense. We postulated that one or more peroxidases produced by Caenorhabditis elegans would act in host defense, possibly in conjunction with BLI-3, the only NOX/DUOX enzyme encoded by the genome that is expressed. Animals exposed to RNA interference (RNAi) of the putative peroxidase genes were screened for susceptibility to the human pathogen Enterococcus faecalis. One of three genes identified, skpo-1 (ShkT-containing peroxidase), was studied in depth. Animals mutant for this gene were significantly more susceptible to E. faecalis, but not Pseudomonas aeruginosa. A slight decrease in longevity was also observed. The skpo-1 mutant animals had a dumpy phenotype of incomplete penetrance; half the animals displayed a dumpy phenotype ranging from slight to severe, and half were morphologically wild type. The SKPO-1 protein contains the critical catalytic residues necessary for peroxidase activity, and in a whole animal assay, more H 2 O 2 was detected from the mutant compared to the wild type, consistent with the loss of an H 2 O 2 sink. By using tissue-specific skpo-1 RNAi and immunohistochemical localization with an anti-SKPO-1 antibody, it was determined that the peroxidase is functionally and physically present in the hypodermis. In conclusion, these results characterize a peroxidase that functions protectively in the hypodermis during exposure to E. faecalis.H EME-containing peroxidases play critical, wide-ranging roles in biological systems. Once called the "animal heme peroxidases," members of the peroxidase-cyclooxgenase superfamily are actually found in all kingdoms of life (Zamocky et al. 2008). The roles of most are poorly characterized, but some are clearly involved in immune defense. For example, the most famous and best-studied member of this group, myeloperoxidase (MPO), is found in the granulocytes of neutrophils where it catalyzes the formation of the potent oxidant HOCl from H 2 O 2 and Cl 2 to kill invading microbes (reviewed by Klebanoff 2005). Another is lactoperoxidase (LPO), which is found on mucosal surfaces and generates the protective oxidant hypothiocyanite (OSCN 2 ) from H 2 O 2 and thiocyanate (SCN 2 ). This process is impaired in the lungs of patients with cystic fibrosis (CF), contributing to the poor clearance of pathogens such as Pseudomonas aeruginosa and Staphylococcus aureus, the most common causes of lung infection in patients with CF (Conner et al. 2002;Geiszt et al. 2003;Forteza et al. 2005;Moskwa et al. 2007).Many of these peroxidases are functionally associated with members of the NADPH oxidase (NOX)/dual oxidase (DUOX) family of proteins. These enzymes generate the H 2 O 2 required as substrate for the peroxidases. For example, N...

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Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans

Cited by 193 publications

References 56 publications

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

Effects and mechanisms of prolongevity induced by Lactobacillus gasseri SBT2055 in Caenorhabditis elegans

Enterococcus faecalis Inhibits Hyphal Morphogenesis and Virulence of Candida albicans

The SKPO-1 Peroxidase Functions in the Hypodermis to ProtectCaenorhabditis elegansFrom Bacterial Infection

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