Proteomics

Dataset Information

47

Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis


ABSTRACT: Tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection remains a huge global public health problem. One striking characteristic of Mtb is its ability to adapt to hypoxia, and thus ensuing transition to dormant state for persistent infection, but how the hypoxia responses of Mtb is regulated remains largely unknown. Here, we performed a quantitative acetylome analysis to compare the acetylation profile of Mtb under aeration and hypoxia, and showed that 377 acetylation sites in 269 proteins of Mtb were significantly change under hypoxia. Especially, deacetylation of Dormancy Survival Regulator (DosR) at K182 promoted the hypoxia response of Mtb and enhanced transcription of DosR-targeted genes. Mechanistically, recombinant DosRK182R protein demonstrated enhanced DNA-binding activity in comparison with DosRK182Q protein. Moreover, Rv0998 was identified as an acetyltransferase that mediates the acetylation of DosR at K182. Deletion of Rv0998 also promoted the adaption of Mtb to hypoxia and transcription of DosR-targeted genes. Mice infected with Mtb strain containing acetylation-defective DosRK182R or lacking Rv0998 had much lower bacterial counts, and less severe histopathological impairments compared with those infected with the wild-type strain. Our findings suggest that hypoxia induces the deacetylation of DosR, which in turn increases its DNA binding ability to promote the transcription of target genes, allowing Mtbto transit to dormancy under hypoxia.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mycobacterium tuberculosis H37Rv  

TISSUE(S): Whole Body

DISEASE(S): Not Available

SUBMITTER: Rachel Green  

LAB HEAD: Baoxue Ge

PROVIDER: PXD008587 | Pride | 2018-10-22

REPOSITORIES: Pride

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Publications

Lysine acetylation of DosR regulates the hypoxia response of Mycobacterium tuberculosis.

Yang Hua H   Sha Wei W   Liu Zhonghua Z   Tang Tianqi T   Liu Haipeng H   Qin Lianhua L   Cui Zhenling Z   Chen Jianxia J   Liu Feng F   Zheng Ruijuan R   Huang Xiaochen X   Wang Jie J   Feng Yonghong Y   Ge Baoxue B  

Emerging microbes & infections 20180321 1


Tuberculosis caused by Mycobacterium tuberculosis (Mtb) infection remains a large global public health problem. One striking characteristic of Mtb is its ability to adapt to hypoxia and trigger the ensuing transition to a dormant state for persistent infection, but how the hypoxia response of Mtb is regulated remains largely unknown. Here we performed a quantitative acetylome analysis to compare the acetylation profile of Mtb under aeration and hypoxia, and showed that 377 acetylation sites in 2  ...[more]

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