CarD is an essential regulator of rRNA transcription required for Mycobacterium tuberculosis persistence.
CarD is an essential regulator of rRNA transcription required for Mycobacterium tuberculosis persistence.
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DOI:
10.1016/j.cell.2009.04.041
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发表时间:
2009-07-10
期刊:
影响因子:
64.5
通讯作者:
Glickman MS
中科院分区:
文献类型:
--
作者:
Stallings CL;Stephanou NC;Chu L;Hochschild A;Nickels BE;Glickman MS
Mycobacterium tuberculosis is arguably the world’s most successful infectious agent due to its ability to control its own cell growth within the host. Bacterial growth rate is closely coupled to rRNA transcription, which in E. coli is regulated through DksA and (p)ppGpp. The mechanisms of rRNA transcriptional control in mycobacteria, which lack DksA, are undefined. Here we identify CarD as an essential mycobacterial protein that controls rRNA transcription. Loss of CarD is lethal for mycobacteria in culture and during infection of mice. CarD depletion leads to sensitivity to killing by oxidative stress, starvation, and DNA damage, accompanied by failure to reduce rRNA transcription. CarD can functionally replace DksA for stringent control of rRNA transcription, even though CarD associates with a distinct site on RNA polymerase. These findings highlight a new molecular mechanism for regulating rRNA transcription in mycobacteria that is critical for M. tuberculosis pathogenesis.
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