title: The PPE2 protein of Mycobacterium tuberculosis translocates to host nucleus and inhibits nitric oxide production.
abstract: Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal. PPE2 was translocated into the macrophage nucleus via the classical importin α/β pathway where it interacted with a GATA-binding site overlapping with the TATA box of inos promoter and inhibited NO production. PPE2 prolonged intracellular survival of a surrogate bacterium M. smegmatis in vitro as well as in vivo. This information are likely to improve our knowledge of host-pathogen interactions during M. tuberculosis infection which is crucial for designing effective anti-TB therapeutics.
authors.affiliation: Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Tuljaguda Complex, Nampally, Hyderabad, India.|Graduate Studies, Manipal University, Manipal, Karnataka, India.
authors.forename: Khalid Hussain
authors.initials: KH
authors.lastname: Bhat
authors.affiliation: Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Tuljaguda Complex, Nampally, Hyderabad, India.|Graduate Studies, Manipal University, Manipal, Karnataka, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Srivastava
authors.affiliation: Molecular Biology Division, National Institute of Nutrition (ICMR), Jamai-Osmania PO, Hyderabad, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Kotturu
authors.affiliation: Molecular Biology Division, National Institute of Nutrition (ICMR), Jamai-Osmania PO, Hyderabad, India.
authors.forename: Sudip
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Laboratory of Molecular Cell Biology, Centre for DNA Fingerprinting and Diagnostics (CDFD), Tuljaguda Complex, Nampally, Hyderabad, India.
authors.forename: Sangita
authors.initials: S
authors.lastname: Mukhopadhyay
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D057131:Immune Evasion; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D020102:Mycobacterium smegmatis / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D000067996:RAW 264.7 Cells; D016385:TATA Box / Q000235:genetics; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D050980:GATA Transcription Factors; C582018:PPE2 protein, Mycobacterium tuberculosis; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II