Open AccessThe activation of the oxidative stress response transcription factor SKN-1 in Caenorhabditis elegans by mitis group streptococci
Author(s) -
Ali Naji,
John B. Houston,
Caroline Skalley Rog,
Ali Al Hatem,
Saba Rizvi,
Ransome van der Hoeven
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0202233
Subject(s) - streptococcus gordonii , streptococcus mitis , biology , caenorhabditis elegans , microbiology and biotechnology , virulence , immunology , streptococcus , genetics , gene , bacteria , antibiotics , streptococcaceae
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 (H 2 O 2 ) 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 H 2 O 2 . Previously, H 2 O 2 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 H 2 O 2 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 H 2 O 2 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 H 2 O 2 produced by S . gordonii . We show during infection, H 2 O 2 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 H 2 O 2 produced by the mitis group and activates the phosphorylation of p38. Additionally, the unfolded protein response plays an important role during infection.