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

The activity of a calmodulin antagonist, trifluoperazine (TFP), was tested in vitro against Mycobacterium avium (ATCC 25291). The minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of this compound for M. avium were 20 and 30 μg/ml, respectively. TFP was also found to completely inhibit the growth of 10 isolates of M. 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% of M. avium within human monocyte-derived macrophages were killed at a drug concentration of 30 μg/ml, which correlates well with the MBC of TFP against M. avium in vitro. Although the MIC for TFP appears to be higher than that for Mycobacterium tuberculosis H₃₇R_v, our studies suggest that calmodulin antagonists might be useful as drugs against infection due to M. avium. It is suggested that administration of TFP in combination with other known drugs may enhance the overall bactericidal effect.