Department of Microbiology and Immunology, Weill Cornell Medicine, 413E 69th Street, New York, New York 10021, USA.
Broad Institute of MIT and Harvard, 415 Main Street, Cambridge, Massachusetts 02142, USA.
Nat Commun. 2017 Mar 28;8:14731. doi: 10.1038/ncomms14731.
Rifampicin, which inhibits bacterial RNA polymerase, provides one of the most effective treatments for tuberculosis. Inhibition of the transcription termination factor Rho is used to treat some bacterial infections, but its importance varies across bacteria. Here we show that Rho of Mycobacterium tuberculosis functions to both define the 3' ends of mRNAs and silence substantial fragments of the genome. Brief inactivation of Rho affects over 500 transcripts enriched for genes of foreign DNA elements and bacterial virulence factors. Prolonged inactivation of Rho causes extensive pervasive transcription, a genome-wide increase in antisense transcripts, and a rapid loss of viability of replicating and non-replicating M. tuberculosis in vitro and during acute and chronic infection in mice. Collectively, these data suggest that inhibition of Rho may provide an alternative strategy to treat tuberculosis with an efficacy similar to inhibition of RNA polymerase.
利福平可抑制细菌 RNA 聚合酶，是治疗结核病最有效的方法之一。抑制转录终止因子 Rho 可用于治疗某些细菌感染，但在不同细菌中的重要性有所不同。在这里，我们发现结核分枝杆菌的 Rho 既可以定义 mRNA 的 3' 末端，又可以沉默基因组的大量片段。Rho 的短暂失活会影响超过 500 个转录本，这些转录本富含外源 DNA 元件和细菌毒力因子的基因。Rho 的长期失活会导致广泛的普遍转录、全基因组反义转录本的增加，以及体外复制和非复制结核分枝杆菌在急性和慢性感染小鼠中的快速丧失活力。总的来说，这些数据表明，抑制 Rho 可能为治疗结核病提供一种替代策略，其疗效与抑制 RNA 聚合酶相似。
