The LuxR family regulator Rv0195 modulates Mycobacterium tuberculosis dormancy and virulence

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• 作者：Haihong Fang ; Dan Yu ; Yuzhi Hong ; Xiaodan Zhou ; Chuanyou Li ; Baolin Sun
• 关键词：Tuberculosis ; Mycobacterium tuberculosis ; Dormancy ; LuxR family transcription factor ; Virulence
• 刊名：Tuberculosis
• 出版年：2013
• 出版时间：July, 2013
• 年：2013
• 卷：93
• 期：4
• 页码：425-431
• 全文大小：731 K

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Summary

Tuberculosis is a leading global killer that has not been effectively controlled to date. The ability of the causative agent, Mycobacterium tuberculosis, to become dormant is one of the major reasons for extended chemotherapeutic regimens and wide epidemicity. The underlying mechanisms of M.?tuberculosis dormancy are not fully understood. In the present work, a LuxR family transcription factor gene, Rv0195, was deleted in the virulent M.?tuberculosis strain H37Rv. Rv0195 deletion did not affect bacterial growth and long-term survival under aerobiosis but decreased cell survival and the ability to rapidly recover from dormancy in an in?vitro anaerobiosis model. The deletion also reduced intracellular survivability under hypoxic and reductive stress triggered by vitamin C. Microarray hybridization analysis showed that Rv0195 affected the expression of more than 180 genes under anaerobiosis, and these genes did not overlap with the known anaerobiosis-up-regulated DosR regulon genes. Furthermore, the Rv0195 deletion diminished bacterial virulence in human macrophage-like cells and resulted in reduced bacterial survival and pathogenicity in a C57BL/6 mouse infection model. These findings offer a novel insight into the mechanisms by which M.?tuberculosis adapts to and recovers from dormancy and demonstrate that the dormancy regulator Rv0195 contributes to bacterial virulence.