Mycobacterium tuberculosis Peptidyl-Prolyl Isomerases Also Exhibit Chaperone like Activity In-Vitro and In-Vivo

• Published in: PloS one Vol. 11; no. 3; p. e0150288
• Main Authors: Pandey, Saurabh, Sharma, Ashish, Tripathi, Deeksha, Kumar, Ashutosh, Khubaib, Mohd, Bhuwan, Manish, Chaudhuri, Tapan Kumar, Hasnain, Seyed Ehtesham, Ehtesham, Nasreen Zafar
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 16.03.2016; Public Library of Science (PLoS)
• Subjects: Apoptosis; Biology; Biology and Life Sciences; Cell cycle; Cell Hypoxia; Cell survival; Chromatography; E coli; Enzymes; Escherichia coli - metabolism; Gel filtration; Gene expression; HEK293 Cells; Humans; Hydrogen peroxide; Hydrophobic and Hydrophilic Interactions; Hydrophobic surfaces; Hypoxia; In Vitro Techniques; Infections; Inflammation; Isomerases; Isomerization; Kinases; Laboratories; Life sciences; Macrophages; Medicine and Health Sciences; Molecular chaperones; Molecular Chaperones - metabolism; Mycobacterium tuberculosis; Mycobacterium tuberculosis - enzymology; Oxidative Stress; Pathology; Peptidylprolyl isomerase; Peptidylprolyl Isomerase - metabolism; Physical Sciences; Physiological aspects; Protein Denaturation; Protein folding; Proteins; Recombinant Proteins - metabolism; Signal transduction; Spectrometry, Fluorescence; Surface Properties; Thermal stress; Tuberculosis; Tumor necrosis factor-TNF; Virulence; Virulence (Microbiology); India
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0150288

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.