The mechanism of the antibacterial selectivity of 2-amino-1, 3, 4-thiadiazole (ATDA) was studied by the incorporation experiments of
14C-nicotinamide and
14C-nicotinic acid into NAD, using ATDA-sensitive
Xanthomonas oryzae and
X. citri, the insensitive
Erwinia carotovora and
Pseudomonas tabaci, and the resistant
X. oryzae strain. In the sensitive bacteria,
14C-NAD was produced from
14C-nicotinamide, but not from
14C-nicotinic acid. The insensitive
E. carotovora utilized both nicotinamide and nicotinic acid as precursors of NAD, but the insensitive
P. tabaci and the resistant strain did not utilize the two precursors.
14C-NAD was also formed from
14C-nicotinamide in the cell extracts from the sensitive strain of
X. oryzae, but not in the extracts from the resistant strain. ATDA is presumably integrated to NAD through the same pathway as nicotinamide in the sensitive bacteria. In the resistant strain, however, ATDA can not be integrated to NAD because of the loss of nicotinamide affinity of the enzymes involving in the synthesis of NAD from nicotinamide or the lack of the enzymes. The insensitivity of
P. tabaci to ATDA also is due to the same mechanism as the resistant strain. In the insensitive
E. carotovora, ATDA may be not integrated to NAD because of the divergent pathway of nicotinamide metabolism in NAD synthesis.
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