Journal article
The activation of the oxidative stress response transcription factor SKN-1 in Caenorhabditis elegans by mitis group streptococci
PloS one, Vol.13(8), pp.e0202233-e0202233
08/16/2018
DOI: 10.1371/journal.pone.0202233
PMCID: PMC6095534
PMID: 30114261
Abstract
The mitis group, a member of the genetically diverse viridans group streptococci, predominately colonizes the human oropharynx. This group has been shown to cause a wide range of infectious complications in humans, including bacteremia in patients with neutropenia, orbital cellulitis and infective endocarditis. Hydrogen peroxide (H2O2) has been identified as a virulence factor produced by this group of streptococci. More importantly, it has been shown that Streptococcus oralis and S. mitis induce epithelial cell and macrophage death via the production of H2O2. Previously, H2O2 mediated killing was observed in the nematode Caenorhabditis elegans in response to S. oralis and S. mitis. The genetically tractable model organism C. elegans is an excellent system to study mechanisms of pathogenicity and stress responses. Using this model, we observed rapid H2O2 mediated killing of the worms by S. gordonii in addition to S. mitis and S. oralis. Furthermore, we observed colonization of the intestine of the worms when exposed to S. gordonii suggesting the involvement of an infection-like process. In response to the H2O2 produced by the mitis group, we demonstrate the oxidative stress response is activated in the worms. The oxidative stress response transcription factor SKN-1 is required for the survival of the worms and provides protection against H2O2 produced by S. gordonii. We show during infection, H2O2 is required for the activation of SKN-1 and is mediated via the p38-MAPK pathway. The activation of the p38 signaling pathway in the presence of S. gordonii is not mediated by the endoplasmic reticulum (ER) transmembrane protein kinase IRE-1. However, IRE-1 is required for the survival of worms in response to S. gordonii. These finding suggests a parallel pathway senses H2O2 produced by the mitis group and activates the phosphorylation of p38. Additionally, the unfolded protein response plays an important role during infection.
Details
- Title: Subtitle
- The activation of the oxidative stress response transcription factor SKN-1 in Caenorhabditis elegans by mitis group streptococci
- Creators
- Ali Naji - The University of Texas Health Science Center at HoustonJohn Houston - The University of Texas Health Science Center at HoustonCaroline Skalley Rog - The University of Texas Health Science Center at HoustonAli Al Hatem - The University of Texas Health Science Center at HoustonSaba Rizvi - The University of Texas Health Science Center at HoustonRansome van der Hoeven - The University of Texas Health Science Center at Houston
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.13(8), pp.e0202233-e0202233
- DOI
- 10.1371/journal.pone.0202233
- PMID
- 30114261
- PMCID
- PMC6095534
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- Public Library Science
- Number of pages
- 19
- Grant note
- University of Texas Health Science Center at Houston, School of Dentistry startup funds P40 OD010440 / NIH Office of Research Infrastructure Programs; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 08/16/2018
- Academic Unit
- Dental Research; Periodontics
- Record Identifier
- 9984738105102771
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