title: The Caenorhabditis elegans p38 MAPK Gene plays a key role in protection from mycobacteria.
abstract: 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.
authors.affiliation: Departments of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas, 77807-3260.
authors.forename: Thushara
authors.initials: T
authors.lastname: Galbadage
authors.affiliation: Departments of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas, 77807-3260.
authors.forename: Tonya F
authors.initials: TF
authors.lastname: Shepherd
authors.affiliation: Departments of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas, 77807-3260.
authors.forename: Suat L G
authors.initials: SL
authors.lastname: Cirillo
authors.affiliation: Department of Biology, Texas Woman's University, Denton, Texas, 76204-5799.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Gumienny
authors.affiliation: Departments of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas, 77807-3260.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Cirillo
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000276:immunology; D017173:Caenorhabditis elegans / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D054637:Dual-Specificity Phosphatases / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics*; D019910:Mycobacterium marinum / Q000276:immunology / Q000472:pathogenicity*; D020102:Mycobacterium smegmatis / Q000276:immunology / Q000472:pathogenicity*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009479:Neuropeptides / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C117509:Dbl-1 protein, C elegans; D051858:Forkhead Transcription Factors; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D034741:RNA, Small Interfering; C439300:Tol-1 protein, C elegans; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C108831:daf-16 protein, C elegans; C073702:skn-1 protein, C elegans; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases; D054637:Dual-Specificity Phosphatases; C501201:VHP-1 protein, C elegans
keywords: C. elegans; Mycobacterium; innate immunity