Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis.
Essential Nucleoid Associated Protein mIHF (Rv1388) Controls Virulence and Housekeeping Genes in Mycobacterium tuberculosis.
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DOI：
10.1038/s41598-018-32340-2
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发表时间：
2018-09-21
影响因子：
4.6
通讯作者：
Cole ST
中科院分区：
文献类型：
--
作者：
Odermatt NT;Sala C;Benjak A;Cole ST
基因表达的严格控制对于结核分枝杆菌适应感染或退出人类细胞时遇到的变化的环境至关重要。虽然已经研究了三种类核相关蛋白（NAPs）EspR、HupB和Lsr2，但第四种即分枝杆菌整合宿主因子（mIHF）的作用仍然难以捉摸。在这里，我们报告了一个多学科的功能分析，利用条件mIHF突变。基因沉默是杀菌性的，导致细长的细胞缺乏隔膜，只有一个类核。ChIP测序确定了分布在染色体周围的153个宽峰，这些峰通常位于EspR也结合的转录起始位点的上游。RNA测序显示209个基因的表达在mIHF消耗后受到严重影响，包括许多tRNA、DNA合成和毒力途径的基因。与NAP功能一致，mIHF通过直接和间接控制发病机制和管家功能所需的基因而充当全局调节剂。
Tight control of gene expression is crucial for Mycobacterium tuberculosis to adapt to the changing environments encountered when infecting or exiting human cells. While three nucleoid associated proteins (NAPs) EspR, HupB and Lsr2 have been investigated, the role of a fourth, the mycobacterial integration host factor (mIHF), remains elusive. Here, we report a multidisciplinary functional analysis that exploits a conditional mIHF mutant. Gene silencing was bactericidal and resulted in elongated cells devoid of septa, with only one nucleoid. ChIP-sequencing identified 153 broad peaks distributed around the chromosome, which were often situated upstream of transcriptional start sites where EspR also bound. RNA-sequencing showed expression of 209 genes to be heavily affected upon mIHF depletion, including those for many tRNAs, DNA synthesis and virulence pathways. Consistent with NAP function, mIHF acts as a global regulator by directly and indirectly controlling genes required for pathogenesis and for housekeeping functions.
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影响因子：
14.9
作者：
Caspi R;Billington R;Ferrer L;Foerster H;Fulcher CA;Keseler IM;Kothari A;Krummenacker M;Latendresse M;Mueller LA;Ong Q;Paley S;Subhraveti P;Weaver DS;Karp PD
通讯作者：
Karp PD
DOI：
10.1073/pnas.0913551107
发表时间：
2010-03-16
影响因子：
11.1
作者：
Gordon, Blair R. G.;Li, Yifei;Liu, Jun
通讯作者：
Liu, Jun
影响因子：
3.2
作者：
Hartkoorn, Ruben C.;Sala, Claudia;Cole, Stewart T.
通讯作者：
Cole, Stewart T.
影响因子：
8.8
作者：
Cortes T;Schubert OT;Rose G;Arnvig KB;Comas I;Aebersold R;Young DB
通讯作者：
Young DB
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK