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System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis
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The effect of treatment with a protease inhibitor on mycobacterial infection

Mohammad Kabbesh1, Ajoy Koomer, Agostino Molteni

  • 1University of Missouri-Kansas City, School of Medicine, Kansas City, MO 64108, USA.

Diagnostic Microbiology and Infectious Disease
|April 6, 2005
PubMed

Insights

Ritonavir, an AIDS drug, reduced Mycobacterium bovis (bacillus Calmette-Guerin, or BCG) infection in rats. This suggests protease inhibitors may offer protection against mycobacterial infections.

Area of Science:

  • Immunology
  • Microbiology
  • Pharmacology

Background:

  • Protease inhibitors, used for AIDS treatment, can cause metabolic effects.
  • Microbial proteases regulate host inflammatory and cellular responses.
  • Mycobacterial infections are common in patients using protease inhibitors.

Purpose of the Study:

  • To evaluate the effect of protease inhibitors on mycobacterial infection.
  • To establish a pilot animal model for studying protease inhibitor impact on infection.
  • To compare Mycobacterium bovis (bacillus Calmette-Guerin, or BCG) infection in rats treated with ritonavir versus controls.

Main Methods:

  • A pilot animal model using Mycobacterium bovis (bacillus Calmette-Guerin, or BCG) infection in rats.
  • Weekly analysis of tissues and serum from drug-treated and control rats.
  • Quantification of acid-fast bacilli (AFBs) using culture, granuloma counts, and staining.

Main Results:

  • Fewer acid-fast bacilli (AFBs) were consistently found in ritonavir-treated rats.
  • Reduced BCG infection was observed across three separate measures: tissue culture, granuloma counts, and tissue staining.
  • Exploration of potential mechanisms included analysis of M. bovis cell wall components and infection-related cytokines.

Conclusions:

  • Ritonavir treatment demonstrated a relative resistance to BCG infection in rats.
  • Further investigation into the mechanisms underlying this observed resistance is warranted.
  • Protease inhibitors may play a role in modulating host response to mycobacterial infections.

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