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Automated Separation of C. elegans Variably Colonized by a Bacterial Pathogen
Published on: March 21, 2014
The Caenorhabditis elegans p38 MAPK Gene plays a key role in protection from mycobacteria
Thushara Galbadage1, Tonya F Shepherd1, Suat L G Cirillo1
1Departments of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas, 77807-3260.
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.
Insights
Caenorhabditis elegans infected with Mycobacterium marinum show high mortality. This study reveals that pathogenic mycobacteria inhibit MAPK-mediated protection, establishing C. elegans as a model for host-pathogen genetic analysis.
Area of Science:
- Microbiology
- Genetics
- Immunology
Background:
- Mitogen-activated protein kinases (MAPK) are crucial for cellular responses to pathogens.
- Investigating MAPK roles in multicellular hosts is challenging due to developmental lethality of mutations.
- Mycobacterium marinum (Mm) serves as a model for tuberculosis.
Purpose of the Study:
- To establish Caenorhabditis elegans as a model for studying host-pathogen interactions in mycobacterial infections.
- To investigate the role of MAPK pathways in C. elegans susceptibility to M. marinum.
- To elucidate mechanisms by which pathogenic mycobacteria evade host immune responses.
Main Methods:
- Infection of C. elegans with pathogenic Mycobacterium marinum and nonpathogenic M. smegmatis.
- Assessment of host mortality and pathological changes.
- Genetic analysis of C. elegans MAPK mutants and other signaling pathways (TOL-like, TGF-β, insulin-like).
- Investigation of MAPK phosphatase gene function in pathogen virulence.
Main Results:
- Mm infection caused >80% mortality in C. elegans, while M. smegmatis caused <15% mortality.
- Pathological changes were observed in Mm-infected C. elegans.
- C. elegans MAPK mutants exhibited hypersusceptibility to mycobacterial infection.
- Pathogenic mycobacteria were found to inhibit MAPK-mediated protection via MAPK phosphatase.
Conclusions:
- Caenorhabditis elegans is a suitable and genetically tractable model for studying mycobacterial pathogenicity and host immune responses.
- MAPK pathways are critical for C. elegans defense against mycobacterial infection.
- Pathogenic mycobacteria actively suppress host MAPK-mediated immunity.
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