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.

AIM:

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.

CONCLUSION:

SEVA TB ES-31 with serine protease and lipase activities may be a potential drug target in tuberculosis management.

• Authors: Anindita Majumdar, Gauri Wankhade, Pranita D Kamble, B C Harinath
• Journal: The Indian journal of tuberculosis (Indian J Tuberc) Vol. 58 Issue 1 Pg. 4-10 (Jan 2011) ISSN: 0019-5707 [Print] India
• PMID: 21442799 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• HIV Protease Inhibitors
• Lactones
• Pyrimidinones
• Lopinavir
• Orlistat
• SEVA TB ES-31 antigen, Mycobacterium tuberculosis
• Serine Endopeptidases
• Ritonavir

Topics

• Antigens, Bacterial (drug effects, metabolism)
• Bacterial Proteins
• Enzyme-Linked Immunosorbent Assay
• HIV Protease Inhibitors (therapeutic use)
• Humans
• Lactones (therapeutic use)
• Lopinavir
• Mycobacterium tuberculosis (drug effects, enzymology, isolation & purification)
• Orlistat
• Pyrimidinones (therapeutic use)
• Ritonavir (therapeutic use)
• Serine Endopeptidases (drug effects, metabolism)
• Tuberculosis (drug therapy, microbiology)