Galbadage Thushara, Shepherd Tonya F, Cirillo Suat L G, Gumienny Tina L, Cirillo Jeffrey D
Departments of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, Texas, 77807-3260.
Department of Biology, Texas Woman's University, Denton, Texas, 76204-5799.
Microbiologyopen. 2016 Jun;5(3):436-52. doi: 10.1002/mbo3.341. Epub 2016 Feb 25.
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.
丝裂原活化蛋白激酶（MAPK）是细胞对病原体反应的关键介质，在感染时被激活，但由于突变导致发育致死，在多细胞宿主中进行研究很困难。海分枝杆菌（Mm）是结核病的既定模型，结核病困扰着世界近三分之一的人口。我们发现，感染Mm的秀丽隐杆线虫死亡率超过80%，但非致病性耻垢分枝杆菌导致的死亡率低于15%。秀丽隐杆线虫感染Mm时会出现病理变化，而Mm突变体导致的死亡率较低，这表明秀丽隐杆线虫是进行详细遗传分析的有前景的毒力模型。秀丽隐杆线虫MAPK突变体对分枝杆菌感染高度敏感；然而，秀丽隐杆线虫的TOL样、TGF-β和胰岛素样信号通路基因在易感性方面不起重要作用。我们表明，致病性分枝杆菌通过MAPK磷酸酶基因抑制MAPK介导的保护作用，并证明秀丽隐杆线虫为宿主和病原体提供了一个遗传上易于处理的致病性模型。
