EspR-dependent ESAT-6 Protein Secretion of Mycobacterium tuberculosis Requires the Presence of Virulence Regulator PhoP.
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
EspR-dependent ESAT-6 Protein Secretion of Mycobacterium tuberculosis Requires the Presence of Virulence Regulator PhoP.
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| Creator |
Anil Kumar, Vijjamarri
Goyal, Rajni Bansal, Roohi Singh, Nisha Sevalkar, Ritesh Rajesh Kumar, Ashwani Sarkar, Dibyendu |
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| Subject |
QR Microbiology
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| Description |
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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| Publisher |
American Society for Biochemistry and Molecular Biology
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| Date |
2016-09-02
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://crdd.osdd.net/open/1852/1/5.pdf
Anil Kumar, Vijjamarri and Goyal, Rajni and Bansal, Roohi and Singh, Nisha and Sevalkar, Ritesh Rajesh and Kumar, Ashwani and Sarkar, Dibyendu (2016) EspR-dependent ESAT-6 Protein Secretion of Mycobacterium tuberculosis Requires the Presence of Virulence Regulator PhoP. The Journal of biological chemistry, 291 (36). pp. 19018-30. ISSN 1083-351X |
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| Relation |
http://www.jbc.org/content/291/36/19018.full.pdf
http://crdd.osdd.net/open/1852/ |
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