Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats.
Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats.
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DOI：
10.1016/j.chom.2021.07.005
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发表时间：
2021-09-08
影响因子：
30.3
通讯作者：
Elde NC
中科院分区：
文献类型：
--
作者：
Carey CM;Apple SE;Hilbert ZA;Kay MS;Elde NC
感染性腹泻病的发病机制归因于肠毒素通过破坏肠道水分吸收而导致脱水。我们研究了哺乳动物鸟苷酸环化酶-C (GC-C) 的遗传变异模式，以确定宿主物种如何适应腹泻感染，GC-C 是一种细菌编码的热稳定肠毒素 (STa) 靶向的肠道受体。我们对 GC-C 的系统发育和功能分析支持灵长类动物和蝙蝠中腹泻细菌长期存在的进化冲突，并且不同物种对 STa 的易感性存在很大差异。在蝙蝠中，我们进一步表明 GC-C 多样化引发了内源性尿鸟苷蛋白配体的补偿性突变，这表明病原体驱动整个信号轴进化的不寻常情况。这些发现共同表明，与腹泻病原体的冲突对哺乳动物肠道生理学的进化产生了深远的影响。进化军备竞赛的研究主要集中在宿主免疫因素和传染性微生物之间的相互作用。凯里等人。描述了腹泻细菌病原体和核心肠道信号轴之间不寻常的遗传冲突，该信号轴对于维持适当的肠道生理机能至关重要，拓宽了病原体驱动进化范围的概念。
The pathogenesis of infectious diarrheal diseases is attributed to enterotoxins that cause dehydration by disrupting intestinal water absorption. We investigated patterns of genetic variation in mammalian Guanylate Cyclase-C (GC-C), an intestinal receptor targeted by bacterially-encoded heat-stable enterotoxins (STa), to determine how host species adapt in response to diarrheal infections. Our phylogenetic and functional analysis of GC-C supports longstanding evolutionary conflict with diarrheal bacteria in primates and bats, with highly variable susceptibility to STa across species. In bats, we further show that GC-C diversification has sparked compensatory mutations in the endogenous uroguanylin ligand, suggesting an unusual scenario of pathogen-driven evolution of an entire signaling axis. Together these findings suggest that conflicts with diarrheal pathogens have had far-reaching impacts on the evolution of mammalian gut physiology. Studies of evolutionary arms-races have primarily focused on interactions between host immune factors and infectious microbes. Carey et al. describe an unusual genetic conflict between diarrheal bacterial pathogens and a core intestinal signaling axis critical for maintaining proper gut physiology, broadening conceptions of the reach of pathogen-driven evolution.
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影响因子：
15.9
作者：
Brook CE;Dobson AP
通讯作者：
Dobson AP
影响因子：
158.5
作者：
Fiskerstrand, Torunn;Arshad, Najla;Knappskog, Per M.
通讯作者：
Knappskog, Per M.
影响因子：
10.7
作者：
Murrell, Ben;Weaver, Steven;Pond, Sergei L. Kosakovsky
通讯作者：
Pond, Sergei L. Kosakovsky
影响因子：
3.7
作者：
Lou E;Fujisawa S;Morozov A;Barlas A;Romin Y;Dogan Y;Gholami S;Moreira AL;Manova-Todorova K;Moore MA
通讯作者：
Moore MA
影响因子：
3.1
作者：
Bolick DT;Medeiros PHQS;Ledwaba SE;Lima AAM;Nataro JP;Barry EM;Guerrant RL
通讯作者：
Guerrant RL