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

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One of the best characterized two-component systems in Mycobacterium tuberculosis is represented by the PhoPR pair, with PhoR being the transmembrane sensor kinase and PhoP playing an essential part in controlling expression of virulence-associated genes, such as those encoding the ESX-1 secretion apparatus. Previous studies showed that mutations in phoP resulted in attenuation in the mouse model of infection, thus providing the basis for the development of a novel live attenuated Mycobacterium tuberculosis vaccine carrying a deletion in phoP which is today in clinical trials. To thoroughly investigate the role of PhoP in M. tuberculosis, we undertook a systems biology approach comprising ChIP-seq and RNA-seq technologies. We demonstrated binding of PhoP to at least 35 targets on the M. tuberculosis chromosome and direct impact on expression of 30 genes, while further amplification of the signal is provided by regulators acting downstream. The strongest binding site was located between rv2395 and PE_PGRS41, where transcription of the non-coding RNA (ncRNA) Mcr7 was demonstrated. Expression of Mcr7 was found to be restricted to M. tuberculosis species and totally silenced in a phoP mutant. Genetics and proteomics approaches proved that Mcr7 controls activity of the Twin Arginine (Tat) secretion system, thus modulating secretion of the immunodominant antigen Ag85 complex and the BlaC beta-lactamase.

Vyšlo v časopise: The PhoP-Dependent ncRNA Mcr7 Modulates the TAT Secretion System in. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004183
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004183

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