The PhoP-Dependent ncRNA Mcr7 Modulates the TAT Secretion System in Mycobacterium tuberculosis

• DOI: 10.1371/journal.ppat.1004183
• Publication Date: 2014-05-29T16:38:58Z
• Authors: Luis Solans; Jesús Gonzalo-Ase...; Claudia Sala; Andrej Benjak; Swapna Uplekar; Jacques Rougemont; Christophe Guilhot; Wladimir Malaga; Carlos Martín; Stewart T. Cole
• Keywords: Regulon; Chromatin immunoprecipitation

The PhoPR two-component system is essential for virulence in Mycobacterium tuberculosis where it controls expression of approximately 2% the genes, including those ESX-1 secretion apparatus, a major determinant. Mutations phoP lead to compromised production pathogen-specific cell wall components and attenuation both ex vivo vivo. Using antibodies against native protein ChIP-seq experiments (chromatin immunoprecipitation followed by high-throughput sequencing) we demonstrated that PhoP binds at least 35 loci on M. genome. regulon comprises several transcriptional regulators as well genes polyketide synthases PE/PPE proteins. Integration results with high-resolution transcriptomic analysis (RNA-seq) revealed 30 directly, whilst regulatory cascades are responsible signal amplification downstream effects through proteins like EspR, which Esx1 function, via regulation espACD operon. most prominent site was located intergenic region between rv2395 PE_PGRS41, mcr7 gene codes small non-coding RNA (ncRNA). Northern blot confirmed absence Mcr7 an mutant low-level ncRNA complex members other than tuberculosis. By means genetic proteomic analyses modulates translation tatC mRNA thereby impacting activity Twin Arginine Translocation (Tat) apparatus. As result, immunodominant Ag85 beta-lactamase BlaC affected, among others. Mcr7, first whose function has been established, therefore represents missing link functions necessary successful infection host.