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Inhibitory and bactericidal activity of the calmodulin antagonist, trifluoperazine, againstMycobacterium avium in vitro and within human monocyte-derived macrophages

  • Tuberculosis
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Abstract

The activity of a calmodulin antagonist, trifluoperazine (TFP), was testedin vitro againstMycobacterium avium (ATCC 25291). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of this compound forM. avium were 20 and 30 μg/ml, respectively. TFP was also found to completely inhibit the growth of 10 isolates ofM. avium (5 patient isolates and 5 environmental isolates) at 30 μg/ml. At near neutral pH (6.8), the MIC of TFP was found to be 20 μg/ml. However, at pH 5.5 (intracellular pH of macrophages), there was a decrease in the inhibitory activity of the compound against this organism. Interestingly, 99.6% ofM. avium within human monocyte-derived macrophages were killed at a drug concentration of 30 μg/ml, which correlates well with the MBC of TFP againstM. avium in vitro. Although the MIC for TFP appears to be higher than that forMycobacterium tuberculosis H37Rv, our studies suggest that calmodulin antagonists might be useful as drugs against infection due toM. avium. It is suggested that administration of TFP in combination with other known drugs may enhance the overall bactericidal effect.

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Authors and Affiliations

  1. Department of Medicine, Division of Pulmonary and Critical Care, University of California, San Diego, 92103-8374, San Diego, CA, U.S.A.

    Savita P. Rao, Patti Ratnakar & Antonino Catanzaro

  2. Department of Biochemistry, University College of Medical Sciences and GTB Hospital, Shahdara, 110 095, Delhi, India

    P. Suryanarayana Murthy

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  1. Savita P. Rao
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  2. Patti Ratnakar
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  3. P. Suryanarayana Murthy
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  4. Antonino Catanzaro
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Rao, S.P., Ratnakar, P., Murthy, P.S. et al. Inhibitory and bactericidal activity of the calmodulin antagonist, trifluoperazine, againstMycobacterium avium in vitro and within human monocyte-derived macrophages. Indian J Clin Biochem 10, 77–84 (1995). https://doi.org/10.1007/BF02871006

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