title: Mycobacterium tuberculosis Peptidyl-Prolyl Isomerases Also Exhibit Chaperone like Activity In-Vitro and In-Vivo.
abstract: Peptidyl-prolyl cis-trans isomerases (Ppiases), also known as cyclophilins, are ubiquitously expressed enzymes that assist in protein folding by isomerization of peptide bonds preceding prolyl residues. Mycobacterium tuberculosis (M.tb) is known to possess two Ppiases, PpiA and PpiB. However, our understanding about the biological significance of mycobacterial Ppiases with respect to their pleiotropic roles in responding to stress conditions inside the macrophages is restricted. This study describes chaperone-like activity of mycobacterial Ppiases. We show that recombinant rPpiA and rPpiB can bind to non-native proteins in vitro and can prevent their aggregation. Purified rPpiA and rPpiB exist in oligomeric form as evident from gel filtration chromatography.E. coli cells overexpressing PpiA and PpiB of M.tb could survive thermal stress as compared to plasmid vector control. HEK293T cells transiently expressing M.tb PpiA and PpiB proteins show increased survival as compared to control cells in response to oxidative stress and hypoxic conditions generated after treatment with H2O2 and CoCl2 thereby pointing to their likely role in adaption under host generated oxidative stress and conditions of hypoxia. The chaperone-like function of these M.tuberculosis cyclophilins may possibly function as a stress responder and consequently contribute to virulence.
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology, New Delhi, India.|Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Professor CR Rao Road, Hyderabad, India.
authors.forename: Saurabh
authors.initials: S
authors.lastname: Pandey
authors.affiliation: Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
authors.forename: Ashish
authors.initials: A
authors.lastname: Sharma
authors.affiliation: Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
authors.forename: Deeksha
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology, New Delhi, India.|Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Professor CR Rao Road, Hyderabad, India.
authors.forename: Mohd
authors.initials: M
authors.lastname: Khubaib
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology, New Delhi, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Bhuwan
authors.affiliation: Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
authors.forename: Tapan Kumar
authors.initials: TK
authors.lastname: Chaudhuri
authors.affiliation: Dr. Reddy's Institute of Life Sciences, University of Hyderabad Campus, Professor CR Rao Road, Hyderabad, India.|Molecular Infection and Functional Biology Laboratory, Kusuma School of Biological Sciences, Indian Institute of Technology, New Delhi, India.
authors.forename: Seyed Ehtesham
authors.initials: SE
authors.lastname: Hasnain
authors.affiliation: Inflammation Biology and Cell Signaling Laboratory, National Institute of Pathology, New Delhi, India.
authors.forename: Nasreen Zafar
authors.initials: NZ
authors.lastname: Ehtesham
mesh_terms: D015687:Cell Hypoxia; D004926:Escherichia coli / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D066298:In Vitro Techniques; D018832:Molecular Chaperones / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000201:enzymology*; D018384:Oxidative Stress; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D011489:Protein Denaturation; D011994:Recombinant Proteins / Q000378:metabolism; D013050:Spectrometry, Fluorescence; D013499:Surface Properties
chemical_list: D018832:Molecular Chaperones; D011994:Recombinant Proteins; D019696:Peptidylprolyl Isomerase