Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria.
Oleoyl coenzyme A regulates interaction of transcriptional regulator RaaS (Rv1219c) with DNA in mycobacteria.
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DOI：
10.1074/jbc.m114.577338
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发表时间：
2014-09-05
期刊：
影响因子：
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通讯作者：
Mukamolova GV
中科院分区：
文献类型：
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作者：
Turapov O;Waddell SJ;Burke B;Glenn S;Sarybaeva AA;Tudo G;Labesse G;Young DI;Young M;Andrew PW;Butcher PD;Cohen-Gonsaud M;Mukamolova GV
背景：RaaS通过控制atp依赖性外排泵的表达介导分枝杆菌在非允许生长条件下的存活。结果：油酰辅酶a调节RaaS转录因子与DNA的结合，从而调节RaaS调控子的表达和RaaS介导的持久性。结论：细菌外排的活性受活跃生长过程中产生的代谢物的调节。意义：外排泵的失调导致持续存在的低代谢活性分枝杆菌的死亡。我们最近发现，由结核分枝杆菌中的Rv1219c和牛分枝杆菌calmett - gusamrin中的bcg_1279c编码的RaaS（抗微生物辅助生存调节因子）在分枝杆菌长时间静止期和小鼠感染期间的存活中起重要作用。在这里，我们证明了长链酰基辅酶a衍生物（油基辅酶a和棕榈酰辅酶a，在较小程度上）调节RaaS与DNA的结合以及编码atp依赖性外排泵的下游基因的表达。此外，外源添加油酸影响RaaS介导的分枝杆菌的生存改善和RaaS调控子的表达。我们的数据表明，长链酰基辅酶a衍生物可以作为细菌代谢状态的生物学指标。外排泵的失调可用于消除不生长的分枝杆菌。
Background: RaaS mediates mycobacterial survival in nonpermissive growth conditions by controlling expression of ATP-dependent efflux pumps. Results: Oleoyl-CoA regulates binding of the RaaS transcription factor to DNA and thus expression of the RaaS regulon and RaaS-mediated persistence. Conclusion: The activity of bacterial efflux is regulated by metabolites that are produced during active growth. Significance: Dysregulation of efflux pumps results in killing of persisting mycobacteria with low metabolic activity. We have recently shown that RaaS (regulator of antimicrobial-assisted survival), encoded by Rv1219c in Mycobacterium tuberculosis and by bcg_1279c in Mycobacterium bovis bacillus Calmette-Guérin, plays an important role in mycobacterial survival in prolonged stationary phase and during murine infection. Here, we demonstrate that long chain acyl-CoA derivatives (oleoyl-CoA and, to lesser extent, palmitoyl-CoA) modulate RaaS binding to DNA and expression of the downstream genes that encode ATP-dependent efflux pumps. Moreover, exogenously added oleic acid influences RaaS-mediated mycobacterial improvement of survival and expression of the RaaS regulon. Our data suggest that long chain acyl-CoA derivatives serve as biological indicators of the bacterial metabolic state. Dysregulation of efflux pumps can be used to eliminate non-growing mycobacteria.