ArticleThe Journal of biological chemistry2016
EspR-dependent ESAT-6 Protein Secretion of Mycobacterium tuberculosis Requires the Presence of Virulence Regulator PhoP.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 59 citations in OpenAlex.
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- Protein Architecture and Composition in Mycobacterium tuberculosis.Advances in experimental medicine and biology · 2026Review
- Bacterial Lysates Modulate Human Macrophage Responses by Inducing BPI Production and Autophagy.Biomolecules · 2025Article
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- Functional Analysis of Promoters, mRNA Cleavage, and mRNA Secondary Structure onPathogens (Basel, Switzerland) · 2024Article
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- Live Attenuated Vaccines against Tuberculosis: Targeting the Disruption of Genes Encoding the Secretory Proteins of Mycobacteria.Vaccines · 2024Review
- The antagonistic transcription factors, EspM and EspN, regulate the ESX-1 secretion system inmBio · 2024Article
- TcrXY is an acid-sensing two-component transcriptional regulator of Mycobacterium tuberculosis required for persistent infection.Nature communications · 2024Article
- Clinically relevant mutations in the PhoR sensor kinase of host-adaptedMicrobiology spectrum · 2023Article
- Dual functioning by the PhoR sensor is a key determinant to Mycobacterium tuberculosis virulence.PLoS genetics · 2023Article
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- Article
- Convergence of two global regulators to coordinate expression of essential virulence determinants ofeLife · 2022Article
- Molecular Connectivity between Extracytoplasmic Sigma Factors and PhoP Accounts for Coupled Mycobacterial Stress Response.Journal of bacteriology · 2022Article
- HupB, a nucleoid-associated protein, is critical for survival ofFrontiers in microbiology · 2022Article
- Type VII secretion systems: structure, functions and transport models.Nature reviews. Microbiology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Attenuation of Mycobacterium bovis BCG strain is related to the loss of the RD1-encoded ESX-1 secretion system. The ESX-1 system secretes virulence factor ESAT-6 that plays a critical role in modulation of the host immune system, which is essential for establishment of a productive infection. Previous studies suggest that among the reasons for attenuation of Mycobacterium tuberculosis H37Ra is a mutation in the phoP gene that interferes with the ESX-1 secretion system and inhibits secretion of ESAT-6. Here, we identify a totally different and distinct regulatory mechanism involving PhoP and transcription regulator EspR on transcriptional control of the espACD operon, which is required for ESX-1-dependent ESAT-6 secretion. Although both of these regulators are capable of influencing espACD expression, we show that activation of espACD requires direct recruitment of both PhoP and EspR at the espACD promoter. The most fundamental insights are derived from the inhibition of EspR binding at the espACD regulatory region of the phoP mutant strain because of PhoP-EspR protein-protein interactions. Based on these results, a model is proposed suggesting how PhoP and EspR protein-protein interactions contribute to activation of espACD expression and, in turn, control ESAT-6 secretion, an essential pathogenic determinant of M. tuberculosis Together, these results have significant implications on the mechanism of virulence regulation of M. tuberculosis.
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