Novel Mycobacterium tuberculosis anti-σ factor antagonists control σF activity by distinct mechanisms
Novel Mycobacterium tuberculosis anti-σ factor antagonists control σF activity by distinct mechanisms
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DOI：
10.1046/j.1365-2958.2002.03135.x
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发表时间：
2002-09-01
影响因子：
3.6
通讯作者：
Gaudreau, L
中科院分区：
文献类型：
--
作者：
Beaucher, J;Rodrigue, S;Gaudreau, L
结核病的病原，结核分枝杆菌，编码13个西格玛因子，以及一些推测的抗和抗西格玛因子。在这里，我们展示了一个先前被证明参与毒力和持久性过程的sigma因子，sigma(F)，可以被抗sigma因子UsfX特异性抑制。重要的是，UsfX的抑制活性反过来可以被两个新的抗-抗-sigma因子负调控。第一种抗-抗-sigma因子似乎受氧化还原电位调节，第二种可能受磷酸化调节，因为通过引入一种被认为模仿抗-抗-sigma因子磷酸化的突变，它变得无功能。这些结果表明，sigma(F)活性可能在翻译后受到至少两种不同途径的调节，以响应不同可能的生理信号，结果与细菌在疾病进展、潜伏期和再激活期间适应不同宿主环境的能力一致。
The aetiological agent of tuberculosis, Mycobacterium tuberculosis, encodes 13 sigma factors, as well as several putative anti-, and anti-anti- sigma factors. Here we show that a sigma factor that has been previously shown to be involved in virulence and persistence processes, sigma(F), can be specifically inhibited by the anti-sigma factor UsfX. Importantly, the inhibitory activity of UsfX, in turn, can be negatively regulated by two novel anti-anti-sigma factors. The first anti-anti-sigma factor seems to be regulated by redox potential, and the second may be regulated by phosphorylation as it is rendered non-functional by the introduction of a mutation that is believed to mimic phosphorylation of the anti-anti-sigma factor. These results suggest that sigma(F) activity might be post-translationally modulated by at least two distinct pathways in response to different possible physiological cues, the outcome being consistent with the bacteria's ability to adapt to diverse host environments during disease progression, latency and reactivation.