Neisseriaceae, a group of bacteria with dihydrofolate reductases, moderately susceptible to trimethoprim.
Dihydrofolate reductases of five species of the family Neisseriaceae were compared by means of inhibition profiles, using several structurally different inhibitors, including trimethoprim (TMP) and pyrimethamine. All enzymes were seen to be highly susceptible to the folate analog aminopterin, but exhibited moderate susceptibility to all other inhibitors tested. Approximately 200-fold higher concentrations of TMP were needed to inhibit neisserial reductases as compared to the E. coli enzyme. Besides poor penetration this is assumed to be the main basis for the low susceptibility of neisseriae to TMP. In addition to TMP all other inhibitors were also moderately active or inactive in vitro. The enzymatic differences, as seen from inhibition profiles, were statistically significant but small among all species of the genus Neisseria. Branhamella catarrhalis on the other hand was seen to be far less related to the other neisseriae, as seen by the inhibition profile of its reductase, its dihydrofolate reductase conttent, as well as by its in vitro properties.
D004352:Drug Resistance, Microbial; D005493:Folic Acid Antagonists; D009346:Neisseriaceae / Q000187:drug effects* / Q000201:enzymology; D013045:Species Specificity; D013449:Sulfonamides / Q000494:pharmacology; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism; D014295:Trimethoprim / Q000494:pharmacology*
D005493:Folic Acid Antagonists; D013449:Sulfonamides; D014295:Trimethoprim; D013762:Tetrahydrofolate Dehydrogenase