Resistance to Folic Acid Analogues in a Strain of Streptococcus faecalis.

Nichol, Charles A.; Zakrzewski, Sigmund F.; Welch, Anthony

doi:10.3181/00379727-83-20332

Cited by 40 publications

(14 citation statements)

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“…The rise in dihydrofolic reductase activity observed in bacteria and mouse leukemia cells after exposure to antifolic agents has been attributed to the selective survival of those cells having a higher initial level of enzyme (11)(12)(13)(14)(15)(16)(17). Several findings in the present study indicate that the mechanism for increased dihydrofolic reductase in leukocytes and erythrocytes of patients after amethopterin treatment is not cell selection, but that enzyme "induction" S actually occurs.…”

Section: Discussionmentioning

confidence: 51%

“…Since the observation that dihydrofolic reductase is powerfully inhibited by the folic acid antagonists aminopterin 1 and amethopterin 2 (6)(7)(8)(9)(10), the development of resistance to these agents has been studied in bacteria (11)(12)(13)(14), cultured cells (15, 16), L-1210 leukemic mice (17), and human leukemia (1,18,19). In each of these instances, exposure of the system to the folic acid antagonists resulted in an increased level of dihydrofolic reductase, suggesting that these events were associated with resistance.…”

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confidence: 99%

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The “Induction” of Dihydrofolic Reductase Activity in Leukocytes and Erythrocytes of Patients Treated With Amethopterin*

Bertino

Donohue²,

Simmons³

et al. 1963

J. Clin. Invest.

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Section: Discussionmentioning

confidence: 51%

mentioning

confidence: 99%

The “Induction” of Dihydrofolic Reductase Activity in Leukocytes and Erythrocytes of Patients Treated With Amethopterin*

Bertino

Donohue²,

Simmons³

et al. 1963

J. Clin. Invest.

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“…Subsequent studies with this strain and with other amethopterin-resistant mutants of this microorganism have shown that a number of nutritional and enzymatic changes contribute to resistance (1,3,6,16,17,23,24). Amethopterin-resistant strains of this microorganism have decreased requirements for folic acid and increased activity in the formation of 5-formyltetrahydrofolate when compared to the parental strain (10,16,17,22).…”

mentioning

confidence: 99%

Dihydrofolate Reductase Activity in Strains of Streptococcus faecium var. durans Resistant to Methasquin and Amethopterin

Rader

Hutchison

1972

J Bacteriol

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Resistance to the antifolates methasquin and amethopterin has been studied in new strains of Streptococcus faecium var. durans. Two methasquin-resistant strains (SF/MQ, SF/MQT) and an amethopterin-resistant strain (SF/AM) were selected independently from the wild-type S. faecium var. durans (SF/0). SF/MQT is a thymine auxotroph. Total dihydrofolate reductase activity was elevated in each of the resistant strains. The greatest increase (36-fold) was observed in extracts of SF/AM. The methasquin-resistant strains, SF/MQ and SF/MQT, had 29-fold and 8-fold, respectively, more dihydrofolate reductase activity than the parental strain. Total dihydrofolate reductase activity of SF/0 was separable by gel filtration into two components: a folate reductase (11%) and a specific dihydrofolate reductase (89%). Folate reductase activity was associated with 88% of the total dihydrofolate reductase activity of SF/MQT, with specific dihydrofolate reductase activity accounting for the remaining 12%. In SF/MQ and SF/AM, folate reductase activity was associated with 97% of the total dihydrofolate reductase activity. Studies of the inhibition by methasquin and amethopterin of partially purified folate reductase and specific dihydrofolate reductase of the mutant strains suggested that resistance was not accompanied by changes in the affinities of these enzymes for either antifolate.

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“…Any hypothesis about a relationship between these two activities would be supported if another compound which produced one of the phenomena also produced the other. With such a possibility in view tests were carried out with L-ascorbic acid which has been reported to increase citrovorum factor production by suspensions and extracts of Streptococcus fucalis R (Broquist et al 1953; Nichol, 1954). When examined L-ascorbic acid ( l o -2~) was found to stimulate synthesis of 123 citrovorum factor from formate and p-aminobenzoic acid and partially prevented inactivation of lO-%-leucovorin by suspensions of L. mesenteroi&eS P 60 variant s t m h , though the effect was not so marked as that produced by CO, ( Table 6).…”

Section: The Replacement Of Cog By ~S C O T~j~c Acidmentioning

confidence: 99%

The Synthesis of Citrovorum Factor by Leuconostoc mesenteroides P 60

CROSS

1960

Journal of General Microbiology

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SUMMARYWhen incubated with p-aminobenzoic acid, formate and glucose, suspensions of a v k a n t strain of ~o n o s t o c meseWoides strain P 60 formed two factors possessing folk acid activity. One of these factors behaved like rhizopterin in supporting the growth of Streptococczcs faecalis strain R but not of Lactobacillus cmei. The other, like leucovorin, supported the growth of Leucmstoc citrovmrn. The synthesis of 'citrovonun factor' was enhanced 5-to 20-fold by the presence of CO, in the gas phase. Sulphathiazole inhibited the synthesis of both factors, the inhibition being overcome competitively by p-aminobenzoic acid. Leucovorin was destroyed by suspensions of L. msenteroides P60 in phosphate-buffered glucose. The diminution of activity for L. citrovmm (decrease of citrovorum factor) was decreased when the incubation was carried out in a C0,-enriched atmosphere. Ascorbic acid, which behaved similarly to CO, in partially preventing inactivation of leucovorin by suspensions of L. me8Woides P60 variant strain, also increased the synthesis of citrovonun factor from formate and p-aminobenzoic acid and partially satisfied the requirement of the growing L. mesenteroides P60 for COB.

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Resistance to Folic Acid Analogues in a Strain of Streptococcus faecalis.

Cited by 40 publications

References 0 publications

The “Induction” of Dihydrofolic Reductase Activity in Leukocytes and Erythrocytes of Patients Treated With Amethopterin*

The “Induction” of Dihydrofolic Reductase Activity in Leukocytes and Erythrocytes of Patients Treated With Amethopterin*

Dihydrofolate Reductase Activity in Strains of Streptococcus faecium var. durans Resistant to Methasquin and Amethopterin

The Synthesis of Citrovorum Factor by Leuconostoc mesenteroides P 60

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