当前位置：
X-MOL 学术
›
PLOS Pathog.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Iron availability and oxygen tension regulate the Yersinia Ysc type III secretion system to enable disseminated infection.
PLoS Pathogens ( IF 5.5 ) Pub Date : 2019-12-23 , DOI: 10.1371/journal.ppat.1008001 Diana Hooker-Romero 1 , Erin Mettert 2 , Leah Schwiesow 3 , David Balderas 1 , Pablo A Alvarez 1 , Anadin Kicin 1 , Azuah L Gonzalez 1 , Gregory V Plano 4 , Patricia J Kiley 2 , Victoria Auerbuch 1
PLoS Pathogens ( IF 5.5 ) Pub Date : 2019-12-23 , DOI: 10.1371/journal.ppat.1008001 Diana Hooker-Romero 1 , Erin Mettert 2 , Leah Schwiesow 3 , David Balderas 1 , Pablo A Alvarez 1 , Anadin Kicin 1 , Azuah L Gonzalez 1 , Gregory V Plano 4 , Patricia J Kiley 2 , Victoria Auerbuch 1
Affiliation
|
The enteropathogen Yersinia pseudotuberculosis and the related plague agent Y. pestis require the Ysc type III secretion system (T3SS) to subvert phagocyte defense mechanisms and cause disease. Yet type III secretion (T3S) in Yersinia induces growth arrest and innate immune recognition, necessitating tight regulation of the T3SS. Here we show that Y. pseudotuberculosis T3SS expression is kept low under anaerobic, iron-rich conditions, such as those found in the intestinal lumen where the Yersinia T3SS is not required for growth. In contrast, the Yersinia T3SS is expressed under aerobic or anaerobic, iron-poor conditions, such as those encountered by Yersinia once they cross the epithelial barrier and encounter phagocytic cells. We further show that the [2Fe-2S] containing transcription factor, IscR, mediates this oxygen and iron regulation of the T3SS by controlling transcription of the T3SS master regulator LcrF. IscR binds directly to the lcrF promoter and, importantly, a mutation that prevents this binding leads to decreased disseminated infection of Y. pseudotuberculosis but does not perturb intestinal colonization. Similar to E. coli, Y. pseudotuberculosis uses the Fe-S cluster occupancy of IscR as a readout of oxygen and iron conditions that impact cellular Fe-S cluster homeostasis. We propose that Y. pseudotuberculosis has coopted this system to sense entry into deeper tissues and induce T3S where it is required for virulence. The IscR binding site in the lcrF promoter is completely conserved between Y. pseudotuberculosis and Y. pestis. Deletion of iscR in Y. pestis leads to drastic disruption of T3S, suggesting that IscR control of the T3SS evolved before Y. pestis split from Y. pseudotuberculosis.
中文翻译：
铁的可用性和氧张力调节耶尔森氏菌Ysc III型分泌系统，以实现弥散性感染。
肠病原性耶尔森氏菌假结核和相关鼠疫耶尔森氏菌需要Ysc III型分泌系统（T3SS）来破坏吞噬细胞防御机制并引起疾病。然而，耶尔森氏菌中的III型分泌（T3S）会导致生长停滞和先天免疫识别，因此必须严格调节T3SS。在这里，我们显示在厌氧，富铁条件下，假结核耶尔森氏菌T3SS表达保持较低水平，例如在不需要内生耶尔森氏菌T3SS的肠腔中发现的情况。相反，耶尔森氏菌T3SS在需氧或厌氧，铁缺乏的条件下表达，例如耶尔森氏菌越过上皮屏障并遇到吞噬细胞时所遇到的条件。我们进一步表明[2Fe-2S]包含转录因子IscR，通过控制T3SS主调节子LcrF的转录来介导T3SS的氧和铁调节。IscR直接与lcrF启动子结合，重要的是，阻止这种结合的突变导致假结核耶尔森氏菌的播散感染减少，但不会干扰肠道定植。与大肠杆菌相似，假结核耶尔森氏菌利用IscR的Fe-S簇占据率来读取影响细胞Fe-S簇稳态的氧和铁条件。我们建议假结核耶尔森氏菌已采用此系统来感应进入更深的组织，并在需要毒力的地方诱导T3S。lcrF启动子中的IscR结合位点在假结核耶尔森氏菌和鼠疫耶尔森氏菌之间是完全保守的。鼠疫耶尔森氏菌中iscR的删除会导致T3S的急剧破坏，
更新日期：2019-12-25
中文翻译：
铁的可用性和氧张力调节耶尔森氏菌Ysc III型分泌系统，以实现弥散性感染。
肠病原性耶尔森氏菌假结核和相关鼠疫耶尔森氏菌需要Ysc III型分泌系统（T3SS）来破坏吞噬细胞防御机制并引起疾病。然而，耶尔森氏菌中的III型分泌（T3S）会导致生长停滞和先天免疫识别，因此必须严格调节T3SS。在这里，我们显示在厌氧，富铁条件下，假结核耶尔森氏菌T3SS表达保持较低水平，例如在不需要内生耶尔森氏菌T3SS的肠腔中发现的情况。相反，耶尔森氏菌T3SS在需氧或厌氧，铁缺乏的条件下表达，例如耶尔森氏菌越过上皮屏障并遇到吞噬细胞时所遇到的条件。我们进一步表明[2Fe-2S]包含转录因子IscR，通过控制T3SS主调节子LcrF的转录来介导T3SS的氧和铁调节。IscR直接与lcrF启动子结合，重要的是，阻止这种结合的突变导致假结核耶尔森氏菌的播散感染减少，但不会干扰肠道定植。与大肠杆菌相似，假结核耶尔森氏菌利用IscR的Fe-S簇占据率来读取影响细胞Fe-S簇稳态的氧和铁条件。我们建议假结核耶尔森氏菌已采用此系统来感应进入更深的组织，并在需要毒力的地方诱导T3S。lcrF启动子中的IscR结合位点在假结核耶尔森氏菌和鼠疫耶尔森氏菌之间是完全保守的。鼠疫耶尔森氏菌中iscR的删除会导致T3S的急剧破坏，
京公网安备 11010802027423号