Activity of the combination of fludalanine and cycloserine against mycobacteria in vitro.
The initial steps in the incorporation of alanine into the bacterial cell wall include the conversion of natural to D-alanine by a racemase followed by the coupling of 2 D-alanine molecules by a synthetase to yield a dipeptide. A combination of fludalanine (3-fluoro-2-deutero-D-alanine), an analogue of D-alanine that irreversibly inactivates the racemase, and cycloserine, which inhibits the synthetase, has been found to be more active against a wide range of non-mycobacterial organisms than either fludalanine or cycloserine alone. When tested against 16 strains of slowly growing mycobacteria including M. tuberculosis, the combination was no more active than cycloserine alone. However the cycloserine minimal inhibitory concentration (MIC) of the combination against the rapidly growing species M. phlei and M. fortuitum was much lower than the MIC of cycloserine alone, particularly with low ratios of fludalanine to cycloserine, and was within the range attainable by therapeutic cycloserine plasma concentrations in man, suggesting its possible use in the treatment of disease due to M. fortuitum.
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003523:Cycloserine / Q000494:pharmacology*; D004338:Drug Combinations; D066298:In Vitro Techniques; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects*
D004338:Drug Combinations; D003523:Cycloserine; C045952:fludalanine; D000409:Alanine