Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death.
Pseudomonas aeruginosa disrupts Caenorhabditis elegans iron homeostasis, causing a hypoxic response and death.
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DOI：
10.1016/j.chom.2013.03.003
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发表时间：
2013-04-17
影响因子：
30.3
通讯作者：
Ausubel FM
中科院分区：
文献类型：
--
作者：
Kirienko NV;Kirienko DR;Larkins-Ford J;Wählby C;Ruvkun G;Ausubel FM
机会致病菌铜绿假单胞菌引起严重的人类感染，但有效的治疗和介导发病机制仍然难以捉摸。秀丽隐杆线虫与人类共享先天免疫途径，这使得它在研究感染方面非常宝贵。为了确定铜绿假单胞菌如何破坏宿主生物学，我们研究了铜绿假单胞菌如何杀死C。elegans在一个液体为基础的发病机制模型。我们发现，铜绿假单胞菌介导的杀伤不需要群体感应途径或宿主定植。化学遗传筛选显示铁螯合剂减轻了铜绿假单胞菌介导的杀伤。与铁在铜绿假单胞菌发病机制中的作用一致，细菌铁载体绿脓菌荧光素是毒力所需的，并且足以在不存在细菌的情况下诱导缺氧反应和死亡。失去了C。elegans缺氧诱导因子HIF-1，调节铁稳态，加剧铜绿假单胞菌的发病机制，进一步连接缺氧和杀伤。由于绿脓菌荧光素对于小鼠的毒力是不可或缺的，因此绿脓菌荧光素介导的缺氧可能与人类发病机制相关。
The opportunistic pathogen Pseudomonas aeruginosa causes serious human infections, but effective treatments and the mechanisms mediating pathogenesis remain elusive. Caenorhabditis elegans shares innate immune pathways with humans, making it invaluable to investigate infection. To determine how P. aeruginosa disrupts host biology, we studied how P. aeruginosa kills C. elegans in a liquid-based pathogenesis model. We found that P. aeruginosa-mediated killing does not require quorum-sensing pathways or host colonization. A chemical genetic screen revealed that iron chelators alleviate P. aeruginosa-mediated killing. Consistent with a role for iron in P. aeruginosa pathogenesis, the bacterial siderophore pyoverdin was required for virulence and was sufficient to induce a hypoxic response and death in the absence of bacteria. Loss of the C. elegans hypoxia-inducing factor HIF-1, which regulates iron homeostasis, exacerbated P. aeruginosa pathogenesis, further linking hypoxia and killing. As pyoverdin is indispensable for virulence in mice, pyoverdin-mediated hypoxia is likely relevant in human pathogenesis.
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影响因子：
3.2
作者：
Chand, Nikhilesh S.;Lee, Jenny See-Wai;Hung, Deborah T.
通讯作者：
Hung, Deborah T.
影响因子：
56.9
作者：
Garsin, DA;Villanueva, JM;Ausubel, FM
通讯作者：
Ausubel, FM
影响因子：
3.1
作者：
Koury, J;Deitch, EA;Feinman, R
通讯作者：
Feinman, R
影响因子：
3.6
作者：
Dietrich, Lars E. P.;Price-Whelan, Alexa;Newman, Dianne K.
通讯作者：
Newman, Dianne K.
影响因子：
3.1
作者：
ANKENBAUER, R;SRIYOSACHATI, S;COX, CD
通讯作者：
COX, CD