title: Towards understanding the biological function of the unusual chaperonin Cpn60.1 (GroEL1) of Mycobacterium tuberculosis.
abstract: The 60 kDa heat shock proteins, also known as Cpn60s (GroELs) are components of the essential protein folding machinery of the cell, but are also dominant antigens in many infectious diseases. Although generally essential for cellular survival, in some organisms such as Mycobacterium tuberculosis, one or more paralogous Cpn60s are known to be dispensable. In M. tuberculosis, Cpn60.2 (GroEL2) is essential for cell survival, but the biological role of the non-essential Cpn60.1 (GroEL1) is still elusive. To understand the relevance of Cpn60.1 (GroEL1) in M. tuberculosis physiology, detailed transcriptomic analyses for the wild type H37Rv and cpn60.1 knockout (groEL1-KO) were performed under in vitro stress conditions: stationary phase, cold shock, low aeration, mild cold shock and low pH. Additionally, the survival of the groEL1-KO was assessed in macrophages at multiplicity of infection (MOI) of 1:1 and 1:5. We observed that survival under low aeration was significantly compromised in the groEL1-KO. Further, the gene expression analyses under low aeration showed change in expression of several key virulence factors like two component system PhoP/R and MprA/B, sigma factors SigM and C and adversely affected known hypoxia response regulators Rv0081, Rv0023 and DosR. Our work is therefore suggestive of an important role of Cpn60.1 (GroEL1) for survival under low aeration by affecting the expression of genes known for hypoxia response.
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500 001, India; Graduate Studies, Manipal University, Manipal 576104, India; National Centre for Cell Science, Ganeshkhind, Pune 411 007, India.
authors.forename: Aditi
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Center for Infectious Diseases Research (formerly known as Seattle Biomedical Research Institute), Seattle, WA, USA.
authors.forename: Tige
authors.initials: T
authors.lastname: Rustad
authors.affiliation: National Centre for Cell Science, Ganeshkhind, Pune 411 007, India.
authors.forename: Gaurang
authors.initials: G
authors.lastname: Mahajan
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Arun
authors.initials: A
authors.lastname: Kumar
authors.affiliation: International Centre for Genetic Engineering and Biotechnology, New Delhi, India.
authors.forename: Kanury V S
authors.initials: KV
authors.lastname: Rao
authors.affiliation: Department of Biochemistry, University of Hyderabad, Hyderabad, India.
authors.forename: Sharmistha
authors.initials: S
authors.lastname: Banerjee
authors.affiliation: Center for Infectious Diseases Research (formerly known as Seattle Biomedical Research Institute), Seattle, WA, USA; University of Washington Department of Global Health, Seattle, WA, USA.
authors.forename: David R
authors.initials: DR
authors.lastname: Sherman
authors.affiliation: Centre for DNA Fingerprinting and Diagnostics, Nampally, Hyderabad 500 001, India; National Centre for Cell Science, Ganeshkhind, Pune 411 007, India. Electronic address: shekhar@nccs.res.in.
authors.forename: Shekhar C
authors.initials: SC
authors.lastname: Mande
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism*; D003080:Cold Temperature; D058639:Cold-Shock Response; D020869:Gene Expression Profiling; D015964:Gene Expression Regulation, Bacterial; D055785:Gene Knockdown Techniques; D006863:Hydrogen-Ion Concentration; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity; D010100:Oxygen / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D037521:Virulence Factors; D010100:Oxygen
keywords: Chaperonin; Cpn60; GroEL; Low aeration; Microarray; Mycobacterium tuberculosis