title: Effect of HIV protease inhibitors and Orlistat on mycobacterial ES-31 serine protease, a potential drug target in Mycobacterium tuberculosis.
abstract: BACKGROUND
  Mycobacterial excretory secretory-31 (SEVA TB ES-31) antigen is shown to possess protease and lipase activities.
  
  
  OBJECTIVE
  To study the effect of commonly used HIV-protease inhibitors and lipase inhibitor Orlistat if any on mycobacterial ES-31 serine protease in vitro enzyme activity and on the growth of M.tb H37Ra bacilli in axenic culture.
  
  
  METHODS
  Effect of HIV-protease inhibitors namely Ritonavir, Lopinavir and Indinavir and Orlistat on protease activity of ES-31 was assessed using azocasein assay and on bacillary growth in axenic culture of Mycobacterium tuberculosis H37Ra. The concentration of ES-31 antigen in culture filtrate was determined by sandwich peroxidase ELISA using anti ES-31 antibody and the growth of bacilli by CFU count.
  
  
  RESULTS
  HIV-protease inhibitors such as Ritonavir, Lopinavir and Indinavir and lipase inhibitor Orlistat inhibited serine protease activity by 41.3 - 69.7% in vitro. These inhibitors also showed decreased bacterial growth in axenic culture and further confirmed by decreased concentration of ES-31 serine protease secretion in the culture fluid. Ritonavir showed maximum inhibition of 77% on the growth of the bacilli in axenic culture while anti obesity drug Orlistat showed 61% inhibition.
  
  
  CONCLUSIONS
  SEVA TB ES-31 with serine protease and lipase activities may be a potential drug target in tuberculosis management.
authors: Department of Biochemistry, JB Tropical Disease Research Centre, MGIMS, Sevagram.
authors: Anindita
authors: A
authors: Majumdar
authors: Gauri
authors: G
authors: Wankhade
authors: Pranita D
authors: PD
authors: Kamble
authors: B C
authors: BC
authors: Harinath
mesh_terms: D000942:Antigens, Bacterial / Q000187:drug effects* / Q000378:metabolism; D001426:Bacterial Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use*; D061466:Lopinavir; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000201:enzymology* / Q000302:isolation & purification; D000077403:Orlistat; D011744:Pyrimidinones / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use; D012697:Serine Endopeptidases / Q000187:drug effects* / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D017320:HIV Protease Inhibitors; D007783:Lactones; D011744:Pyrimidinones; D061466:Lopinavir; D000077403:Orlistat; C541122:SEVA TB ES-31 antigen, Mycobacterium tuberculosis; D012697:Serine Endopeptidases; D019438:Ritonavir