A response regulator promotes Francisella tularensis intramacrophage growth by repressing an anti-virulence factor.
A response regulator promotes Francisella tularensis intramacrophage growth by repressing an anti-virulence factor.
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DOI：
10.1111/mmi.13418
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发表时间：
2016-08
影响因子：
3.6
通讯作者：
Dove SL
中科院分区：
文献类型：
--
作者：
Ramsey KM;Dove SL
孤儿反应调节剂PmrA对土拉弗朗西斯菌的巨噬细胞生长和存活至关重要。PmrA被认为通过直接结合Francisella Pathogenicity Island （FPI）上的启动子并正向调节FPI基因的表达来促进巨噬细胞内生长，FPI基因编码巨噬细胞生长所需的VI型分泌系统。利用ChIP-Seq和RNA-Seq，我们确定了土拉菌染色体上被PmrA占据的区域和受PmrA调节的基因。我们发现PmrA与土拉菌染色体的252个不同区域相关，但仅在这些位置中的少数位置发挥调节作用。我们提出的证据表明，PmrA不是直接作为FPI基因表达的激活剂，而是通过抑制单个靶基因priM （PmrA抑制的巨噬细胞内生长抑制剂）的表达来促进巨噬细胞内生长。因此，我们的研究结果表明，PmrA在促进细胞内生长中的作用是抑制一种以前未知的抗毒因子。PriM是第一个被描述的细菌编码因子，可以干扰巨噬细胞内的生长和土拉菌的存活。
The orphan response regulator PmrA is essential for the intramacrophage growth and survival of Francisella tularensis. PmrA was thought to promote intramacrophage growth by binding directly to promoters on the Francisella Pathogenicity Island (FPI) and positively regulating the expression of FPI genes, which encode a Type VI secretion system required for intramacrophage growth. Using both ChIP-Seq and RNA-Seq we identify those regions of the F. tularensis chromosome occupied by PmrA and those genes that are regulated by PmrA. We find that PmrA associates with 252 distinct regions of the F. tularensis chromosome, but exerts regulatory effects at only a few of these locations. Rather than by functioning directly as an activator of FPI gene expression we present evidence that PmrA promotes intramacrophage growth by repressing the expression of a single target gene we refer to as priM (PmrA-repressed inhibitor of intramacrophage growth). Our findings thus indicate that the role of PmrA in facilitating intracellular growth is to repress a previously unknown anti-virulence factor. PriM is the first bacterially-encoded factor to be described that can interfere with the intramacrophage growth and survival of F. tularensis.
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影响因子：
6.4
作者：
Jorth P;Turner KH;Gumus P;Nizam N;Buduneli N;Whiteley M
通讯作者：
Whiteley M
影响因子：
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作者：
Russell AB;Wexler AG;Harding BN;Whitney JC;Bohn AJ;Goo YA;Tran BQ;Barry NA;Zheng H;Peterson SB;Chou S;Gonen T;Goodlett DR;Goodman AL;Mougous JD
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作者：
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影响因子：
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作者：
Clemens DL;Ge P;Lee BY;Horwitz MA;Zhou ZH
通讯作者：
Zhou ZH
DOI：
10.1073/pnas.1500989112
发表时间：
2015-04-21
影响因子：
11.1
作者：
Pontes, Mauricio H.;Lee, Eun-Jin;Groisman, Eduardo A.
通讯作者：
Groisman, Eduardo A.