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The RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation


Borrelia burgdorferi, the spirochete responsible for causing Lyme disease, is maintained in nature via cycling between an Ixodes tick vector and a vertebrate host. The spirochete must adapt to and survive extreme nutrient deprivation, which may last months between blood meals, to persist in the midgut of the tick vector. How B. burgdorferi survives extended periods under such nutrient limitations has not been previously examined. In this study, we demonstrated that the stringent response, governed by RelBbu, which synthesizes and hydrolyzes the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), is necessary for persistence in the tick. RelBbu was also required for survival during in vitro starvation and relBbu mutants more readily formed round bodies, a morphological change recently implicated in persistence in the tick. These adaptations to nutrient limitations appear to be mediated by global changes in gene expression modulated by RelBbu activity. Our results highlight an important role for RelBbu, and presumably (p)ppGpp, in vivo for persistence of a pathogen in its arthropod vector.


Vyšlo v časopise: The RelA/SpoT Homolog and Stringent Response Regulate Survival in the Tick Vector and Global Gene Expression during Starvation. PLoS Pathog 11(9): e32767. doi:10.1371/journal.ppat.1005160
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005160

Souhrn

Borrelia burgdorferi, the spirochete responsible for causing Lyme disease, is maintained in nature via cycling between an Ixodes tick vector and a vertebrate host. The spirochete must adapt to and survive extreme nutrient deprivation, which may last months between blood meals, to persist in the midgut of the tick vector. How B. burgdorferi survives extended periods under such nutrient limitations has not been previously examined. In this study, we demonstrated that the stringent response, governed by RelBbu, which synthesizes and hydrolyzes the alarmones guanosine tetraphosphate and guanosine pentaphosphate (collectively termed (p)ppGpp), is necessary for persistence in the tick. RelBbu was also required for survival during in vitro starvation and relBbu mutants more readily formed round bodies, a morphological change recently implicated in persistence in the tick. These adaptations to nutrient limitations appear to be mediated by global changes in gene expression modulated by RelBbu activity. Our results highlight an important role for RelBbu, and presumably (p)ppGpp, in vivo for persistence of a pathogen in its arthropod vector.


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