近日,，來自耶魯大學(xué)的研究者表示,，致病菌擁有一些類似于傳感器的結(jié)構(gòu)來激活毒性因子的表達(dá),，進(jìn)而引發(fā)諸如食物中毒或者結(jié)核病等疾病,。這或許為開發(fā)抵御疾病感染的新藥或者新的療法提供一些思路。
研究者Groisman表示,，永遠(yuǎn)不會(huì)有一個(gè)地方?jīng)]有沙門氏菌,，該菌在許多動(dòng)物宿主中存在，當(dāng)然你可以盡量避免沙門氏菌或者學(xué)會(huì)如何抵御沙門氏菌的感染,。每年成千上萬人死于沙門氏菌引發(fā)的食物中毒,，好幾千萬人會(huì)遭遇該菌的感染,，沙門氏菌是一個(gè)公眾危害的主要病菌,。
研究者揭示了是否外部信號可以引發(fā)沙門氏菌自身毒性因子的表達(dá)，研究者研究了巨噬細(xì)胞吞噬沙門氏菌后所發(fā)生分子鏈反應(yīng),，巨噬細(xì)胞是可以對細(xì)菌侵入機(jī)體做出有效反應(yīng)的免疫細(xì)胞,，當(dāng)沙門氏菌被吞噬以后，其會(huì)快速再生,，然后逃過免疫系統(tǒng)監(jiān)視,，進(jìn)而繼續(xù)引發(fā)感染。
研究者刊登在Nature上的文章發(fā)現(xiàn)了環(huán)境并不是引發(fā)沙門氏菌毒性因子表達(dá)的直接威脅,，而沙門氏菌周圍酸度水平的變化會(huì)引發(fā)菌體ATP水平的增加,，ATP的增加可以激活菌體毒力因子的表達(dá)，這樣使得沙門氏菌可以在宿主內(nèi)引發(fā)感染并且不斷寄生在宿主身上,。
在細(xì)菌變得非常有毒性之前,，內(nèi)部的傳感器協(xié)同其它必要的因子都扮演著重要作用，理解這些過程將幫助科學(xué)家開發(fā)出新的防御沙門氏菌感染的武器,。（生物谷Bioon.com）
編譯自：Internal cellular sensors make Salmonella dangerous: study
doi:10.1038/nature11090
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PMID:
Control of a Salmonella virulence locus by an ATP-sensing leader messenger RNA
Eun-Jin Lee & Eduardo A. Groisman
The facultative intracellular pathogen Salmonella enterica resides within a membrane-bound compartment inside macrophages1. This compartment must be acidified for Salmonella to survive within macrophages2, possibly because acidic pH promotes expression of Salmonella virulence proteins3, 4. We reasoned that Salmonella might sense its surroundings have turned acidic not only upon protonation of the extracytoplasmic domain of a protein sensor5 but also by an increase in cytosolic ATP levels, because conditions that enhance the proton gradient across the bacterial inner membrane stimulate ATP synthesis6, 7. Here we report that an increase in cytosolic ATP promotes transcription of the coding region for the virulence gene mgtC, which is the most highly induced horizontally acquired gene when Salmonella is inside macrophages8. This transcript is induced both upon media acidification and by physiological conditions that increase ATP levels independently of acidification. ATP is sensed by the coupling/uncoupling of transcription of the unusually long mgtC leader messenger RNA and translation of a short open reading frame located in this region. A mutation in the mgtC leader messenger RNA that eliminates the response to ATP hinders mgtC expression inside macrophages and attenuates Salmonella virulence in mice. Our results define a singular example of an ATP-sensing leader messenger RNA. Moreover, they indicate that pathogens can interpret extracellular cues by the impact they have on cellular metabolites.
