title: A transcriptional co-repressor regulatory circuit controlling the heat-shock response of Mycobacterium tuberculosis.
abstract: The co-ordinated regulation of heat shock proteins is critically important for the stress response of M. tuberculosis, failure of which results in enhanced immune recognition of the tubercle bacilli with reduced survival during chronic infections. In this study, we show that PhoP regulates the transcription of α-crystallin 2 (acr2), expression of which increases more than any other gene of M. tuberculosis during heat-shock or following macrophage infection. We also show that regulation of acr2 by PhoP is attributable to direct regulator-promoter interactions at specific sites proximal to a sequence motif comprising the target site of another virulence factor, HspR. While both these regulators, on their own, are capable of influencing acr2 expression, remarkably our results show that the two virulence regulators PhoP and HspR interact with each other to influence their in vivo recruitment at the acr2 regulatory region, and in turn, contribute to stress-specific regulation of acr2 expression. We propose a model to suggest how protein-protein interactions between PhoP and HspR influence the regulation of α-crystallin 2, an essential pathogenic determinant of M. tuberculosis.
authors.affiliation: CSIR-Institute of Microbial Technology, Sector 39 A, Chandigarh, 160036, India.
authors.forename: Ranjeet
authors.initials: R
authors.lastname: Singh
authors.forename: Vijjamarri
authors.initials: V
authors.lastname: Anil Kumar
authors.forename: Arijit Kumar
authors.initials: AK
authors.lastname: Das
authors.forename: Roohi
authors.initials: R
authors.lastname: Bansal
authors.forename: Dibyendu
authors.initials: D
authors.lastname: Sarkar
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D056970:Co-Repressor Proteins / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D053263:Gene Regulatory Networks; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D012097:Repressor Proteins / Q000378:metabolism*; D038201:alpha-Crystallins / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D056970:Co-Repressor Proteins; D006360:Heat-Shock Proteins; C108444:HspR protein, bacteria; D012097:Repressor Proteins; D038201:alpha-Crystallins; C500452:alpha-crystallin 2, Mycobacterium tuberculosis; C061064:PhoP protein, Bacteria