title: Interaction of Erp Protein of Mycobacterium tuberculosis with Rv2212 Enhances Intracellular Survival of Mycobacterium smegmatis.
abstract: The Mycobacterium tuberculosis exported repetitive protein (RvErp) is a crucial virulence-associated factor as determined by its role in the survival and multiplication of mycobacteria in cultured macrophages and in vivo Although attempts have been made to understand the function of Erp protein, its exact role in Mycobacterium pathogenesis is still elusive. One way to determine this is by searching for novel interactions of RvErp. Using a yeast two-hybrid assay, an adenylyl cyclase (AC), Rv2212, was found to interact with RvErp. The interaction between RvErp and Rv2212 is direct and occurs at the endogenous level. The Erp protein of Mycobacterium smegmatis (MSMEG_6405, or MsErp) interacts neither with Rv2212 nor with Ms_4279, the M. smegmatis homologue of Rv2212. Deletion mutants of Rv2212 revealed its adenylyl cyclase domain to be responsible for the interaction. RvErp enhances Rv2212-mediated cyclic AMP (cAMP) production. Also, the biological significance of the interaction between RvErp and Rv2212 was demonstrated by the enhanced survival of M. smegmatis within THP-1 macrophages. Taken together, these studies address a novel mechanism by which Erp executes its function.
  
  
  
  RvErp is one of the important virulence factors of M. tuberculosis This study describes a novel function of RvErp protein of M. tuberculosis by identifying Rv2212 as its interacting protein. Rv2212 is an adenylyl cyclase (AC) and produces cAMP, one of the prime second messengers that regulate the intracellular survival of mycobacteria. Therefore, the significance of investigating novel interactions of RvErp is paramount in unraveling the mechanisms governing the intracellular survival of mycobacteria.
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Arsheed Ahmad
authors.initials: AA
authors.lastname: Ganaie
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Garima
authors.initials: G
authors.lastname: Trivedi
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Amanpreet
authors.initials: A
authors.lastname: Kaur
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Sidharth Shankar
authors.initials: SS
authors.lastname: Jha
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Shashi
authors.initials: S
authors.lastname: Anand
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Vibhuti
authors.initials: V
authors.lastname: Rana
authors.affiliation: Drug Target Discovery and Development Division, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Singh
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India.
authors.forename: Shekhar
authors.initials: S
authors.lastname: Kumar
authors.affiliation: CSIR-Institute of Microbial Technology, Chandigarh, India chash71@yahoo.com.
authors.forename: Charu
authors.initials: C
authors.lastname: Sharma
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000382:microbiology; D050296:Microbial Viability; D009165:Mycobacterium Infections, Nontuberculous / Q000382:microbiology*; D020102:Mycobacterium smegmatis / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D011485:Protein Binding; D014376:Tuberculosis / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D000242:Cyclic AMP; D000262:Adenylyl Cyclases