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R L Then

Publications and source records attributed to R L Then.

5 recordsLinked to original sources
PubMed1979

Low trimethoprim susceptibility of anaerobic bacteria due to insensitive dihydrofolate reductases.

All the 28 Bacteroides fragilis strains investigated were susceptible to sulfamethoxazole (minimal inhibitory concentration < 16 mug/ml) and resistant to trimethoprim (TMP; minimal inhibitory concentration > 4 mug/ml). Synergism between sulfamethoxazole and TMP was present in all strains at a ratio of 1:1. The few clostridia investigated proved more resistant to both compounds. Dihydrofolate reductases from B. fragilis, C. perfringens, and some other anaerobic species were isolated. Inhibition profiles with six structurally different inhibitors revealed major differences in all enzymes. For 50% inhibition, the enzyme from B. fragilis and all clostridia required concentrations of TMP which were between several hundredfold and 1,000-fold higher than those required for the enzyme of Escherichia coli, whereas the enzyme from Propionibacterium acnes only needed a threefold higher concentration. In vitro activities of TMP were seen to correspond to the activity at the enzymatic level in B. fragilis and P. acnes, but correspond to a much lesser extent to the activity at the enzymatic level in clostridia, where a poor penetration is assumed to be involved. Dihydrofolate reductase inhibitors other than TMP were found to be as active as TMP both at the enzyme and in vitro. In B. fragilis, higher concentrations of exogenous thymidine were required for increasing the minimal inhibitory concentration of TMP than in E. coli and probably also in C. perfringens.

Anaerobiosis↗
PubMed1979

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.

Drug Resistance, Microbial↗
PubMed1978

Dihydrofolate reductases in some folate-requiring bacteria with low trimethoprim susceptibility.

Dihydrofolate reductases from the folate-requiring strains Streptococcus faecalis ATCC 8043, Lactobacillus casei ATCC 7496, and Pediococcus cerevisiae ATCC 8081, as well as from Lactobacillus arabinosus, which is not dependent on exogenous folate, were isolated, and their properties were compared to reductases of Escherichia coli B, Staphylococcus aureus, and rat liver reductase. An inhibition profile with six different inhibitors revealed significant differences among all enzymes. All lactobacilli reductases are less sensitive to trimethoprim than the enzymes of E. coli and S. aureus, the reductase of P. cerevisiae requiring a concentration at least 1,000 times higher for 50% inhibition. Inhibition of growth of S. faecalis by pyrimethamine and 2,4-diamino-6,7-diisopropyl-pteridine was seen to be much stronger than was predicted from the enzymatic data.

Bacteria↗