Open AccessThe Caenorhabditis elegans p38 MAPK Gene plays a key role in protection from mycobacteria
Author(s) -
Galbadage Thushara,
Shepherd Tonya F.,
Cirillo Suat L. G.,
Gumienny Tina L.,
Cirillo Jeffrey D.
Publication year - 2016
Publication title -
microbiologyopen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.881
H-Index - 36
ISSN - 2045-8827
DOI - 10.1002/mbo3.341
Subject(s) - caenorhabditis elegans , biology , mutant , gene , mapk/erk pathway , mycobacterium smegmatis , genetics , virulence , population , model organism , protein kinase a , kinase , mycobacterium tuberculosis , microbiology and biotechnology , tuberculosis , medicine , demography , pathology , sociology
Mitogen‐activated protein kinases (MAPK) are critical mediators of cellular responses to pathogens and are activated in response to infection, but investigation is difficult in multi‐cell hosts due to developmental lethality of mutations. Mycobacterium marinum ( Mm ) is an established model for tuberculosis, a disease afflicting nearly one‐third of the world's population. We found that Mm ‐infected Caenorhabditis elegans display >80% mortality, but nonpathogenic M. smegmatis cause <15% mortality. C. elegans display pathological changes when infected with Mm, whereas Mm mutants produce lower mortality, suggesting that C. elegans is a promising virulence model for detailed genetic analysis. C. elegans MAPK mutants are hypersusceptible to mycobacterial infection; however, the C. elegans TOL‐like, TGF‐ β and insulin‐like pathway genes do not play important roles in susceptibility. We show that pathogenic mycobacteria inhibit MAPK‐mediated protection through the MAPK phosphatase gene and demonstrate that C. elegans provide a genetically tractable pathogenicity model of both the host and pathogen.