Reporter gene technology to assess activity of antimycobacterial agents in macrophages.

Reporter strains of Mycobacterium tuberculosis and Mycobacterium bovis BCG endogenously expressing firefly luciferase were used in bioluminescence assays to evaluate the activities of isoniazid and rifampin against mycobacteria sequestered in human macrophages. This methodology allowed the efficacy of antibiotics against intracellular mycobacteria to be assessed without the labor-intensive procedures and protracted incubation requirements associated with conventional CFU determinations.

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β-Glucans inhibit intracellular growth of Mycobacterium bovis BCG but not virulent Mycobacterium tuberculosis in human macrophages

Microbial Pathogenesis ◽

10.1016/j.micpath.2011.06.006 ◽

2011 ◽

Vol 51 (4) ◽

pp. 233-242 ◽

Cited By ~ 9

Author(s):

Bret E. Betz ◽

Abul K. Azad ◽

Jessica D. Morris ◽

Murugesan V.S. Rajaram ◽

Larry S. Schlesinger

Keyword(s):

Mycobacterium Tuberculosis ◽

Mycobacterium Bovis ◽

Intracellular Growth ◽

Human Macrophages ◽

Mycobacterium Bovis Bcg

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Culture and Detection of Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (BCG)

BIO-PROTOCOL ◽

10.21769/bioprotoc.49 ◽

2012 ◽

Vol 2 (1) ◽

Author(s):

Ran Chen

Keyword(s):

Mycobacterium Tuberculosis ◽

Mycobacterium Bovis ◽

Mycobacterium Bovis Bcg

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Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens

Molecular Microbiology ◽

10.1046/j.1365-2958.1999.01549.x ◽

2002 ◽

Vol 33 (6) ◽

pp. 1103-1117 ◽

Cited By ~ 229

Author(s):

P. R. Jungblut ◽

U. E. Schaible ◽

H.-J. Mollenkopf ◽

U. Zimny-Arndt ◽

B. Raupach ◽

...

Keyword(s):

Mycobacterium Tuberculosis ◽

Functional Genomics ◽

Mycobacterium Bovis ◽

Proteome Analysis ◽

Microbial Pathogens ◽

Mycobacterium Bovis Bcg

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Ion Transport Modulators as Antimycobacterial Agents

Tuberculosis Research and Treatment ◽

10.1155/2020/3767915 ◽

2020 ◽

Vol 2020 ◽

pp. 1-7

Author(s):

Steven C. Mitini-Nkhoma ◽

Narmada Fernando ◽

G. K. D. Ishaka ◽

Shiroma M. Handunnetti ◽

Sisira L. Pathirana

Keyword(s):

Synergistic Effect ◽

Ion Transport ◽

Mycobacterium Bovis ◽

Bactericidal Activity ◽

Therapeutic Interventions ◽

Intracellular Bacteria ◽

Clearance Rates ◽

Mycobacterium Bovis Bcg ◽

Antimycobacterial Agents ◽

Drug Free

There is an urgent need for better and safer therapeutic interventions for tuberculosis (TB). We assessed the effects of FDA-approved ion transport modulators, namely, ambroxol HCl, amiloride HCl, diazoxide, digoxin, furosemide, hydrochlorothiazide (HCTZ), metformin, omeprazole, pantoprazole, phenytoin, verapamil, and drug X and Y on the growth of free and intracellular Mycobacterium bovis BCG. Free and intracellular M. bovis BCG were cultured in the presence or absence of the test drugs for 3 to 9 days and then quantified. For both free and intracellular bacteria, cultures that were exposed to furosemide, phenytoin, or drug Y yielded lower bacteria counts compared to drug-free controls ( p < 0.05 ). The same was observed with diazoxide, HCTZ, verapamil, and drug X, but only for intracellular M. bovis BCG ( p < 0.05 ). To assess the effects of the drugs on bactericidal activity of rifampicin, free and intracellular M. bovis BCG were treated with rifampicin alone or in combination with each of the thirteen test drugs for 3 to 9 days. For extracellular bacteria, higher bacteria clearance rates were observed in cultures exposed to rifampicin in combination with amiloride HCl, diazoxide, digoxin, furosemide, HCTZ, metformin, pantoprazole, phenytoin, drug X, or drug Y than those exposed to rifampicin alone, indicating that rifampicin had a synergistic effect with these test drugs. Rifampicin was also synergistic with ambroxol HCl, diazoxide, digoxin, furosemide, HCTZ, omeprazole, pantoprazole, phenytoin, verapamil, and drug X against intracellular M. bovis BCG. The antimycobacterial properties exhibited by the ion transport modulators in this study make them viable candidates as adjuncts to the current anti-TB regimens.

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