Discussion
In this study we clearly showed the dose-dependent inhibition
of the M. tuberculosis complex by agents conventionally called
immune suppressants, immune modulators, and growth enhancers,
and vitamins A and D, in part reproducing previous
publications by ourselves and others. The most obvious concern
about any inferences that could be drawn from this study is that
pathogenic M. tuberculosis strains were not evaluated. Our
unfunded laboratory is approved for biosafety level 2 experiments;
hence our study was limited to two biosafety level 2 representatives
of the M. tuberculosis complex. The results presented cannot
be ascribed to a simple pH effect for two reasons. First the
experimental control always contained the same exact concentration
of the dissolving solution as did each vial, irrespective of the
amount of agent being tested. Second, because of buffering, in the
final incubation vial, the pH was always within the manufacturer’s
recommended range of 6.6 0.2 (data not presented).
The experimental inhibitory controls used in this study were
PAS40 and isoniazid,41 both acknowledged anti-tuberculosis
antibiotics. The non-inhibitory control was the intact molecule
of sulfasalazine comprising two molecules, sulfapyridine and 5-
ASA.16 Neither intact sulfasalazine nor 5-ASA inhibited the M.
tuberculosis complex, although we reproduced our subtle bacteriostatic
dose-dependent 5-ASA inhibition of MAP (Tables 3 and 5
and Greenstein et al.23). In contrast, sulfapyridine showed dosedependent
inhibition, more pronounced with BCG than M.
tuberculosis. From our inhibition curves, we conclude that
sulfapyridine is not likely to be clinically useful in the therapy
of MDR tuberculosis and 5-ASA has no potential role.
DiscussionIn this study we clearly showed the dose-dependent inhibitionof the M. tuberculosis complex by agents conventionally calledimmune suppressants, immune modulators, and growth enhancers,and vitamins A and D, in part reproducing previouspublications by ourselves and others. The most obvious concernabout any inferences that could be drawn from this study is thatpathogenic M. tuberculosis strains were not evaluated. Ourunfunded laboratory is approved for biosafety level 2 experiments;hence our study was limited to two biosafety level 2 representativesof the M. tuberculosis complex. The results presented cannotbe ascribed to a simple pH effect for two reasons. First theexperimental control always contained the same exact concentrationof the dissolving solution as did each vial, irrespective of theamount of agent being tested. Second, because of buffering, in thefinal incubation vial, the pH was always within the manufacturer’srecommended range of 6.6 0.2 (data not presented).The experimental inhibitory controls used in this study werePAS40 and isoniazid,41 both acknowledged anti-tuberculosisantibiotics. The non-inhibitory control was the intact moleculeof sulfasalazine comprising two molecules, sulfapyridine and 5-ASA.16 Neither intact sulfasalazine nor 5-ASA inhibited the M.tuberculosis complex, although we reproduced our subtle bacteriostaticdose-dependent 5-ASA inhibition of MAP (Tables 3 and 5and Greenstein et al.23). In contrast, sulfapyridine showed dosedependent
inhibition, more pronounced with BCG than M.
tuberculosis. From our inhibition curves, we conclude that
sulfapyridine is not likely to be clinically useful in the therapy
of MDR tuberculosis and 5-ASA has no potential role.
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