What question did this study set out to answer?

To establish reliable in vitro susceptibility testing methods and evaluate folate utilization and antifolate drug resistance mechanisms in Plasmodium falciparum.

April 1, 1985Antimicrobial Agents and Chemotherapy

In vitro activities of and mechanisms of resistance to antifol antimalarial drugs

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Authors

WMWilbur K. MilhousUniversity of Geneva NWNorman F. WeatherlyUniversity of North Carolina at Chapel Hill JBJean H. BowdreUniversity of North Carolina Hospitals

Discussion

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Implication

In vitro study reveals that exogenous folates antagonize antifol antimalarials in Plasmodium falciparum, indicating complex mechanisms underlying drug resistance.

Key Points

To establish reliable in vitro susceptibility testing methods and evaluate folate utilization and antifolate drug resistance mechanisms in Plasmodium falciparum.
Cultured four isolates of Plasmodium falciparum in standard medium as well as medium depleted of folic acid and p-aminobenzoic acid (PABA).
Assessed the in vitro antimalarial activity of sulfonamides and dihydrofolate reductase inhibitors in the presence and absence of exogenous folates and PABA.
Three of four P. falciparum isolates were successfully propagated and maintained in culture medium depleted of both folic acid and PABA.
The antimalarial potency of sulfonamides and dihydrofolate reductase inhibitors was variably antagonized by the addition of folic acid and PABA to the medium.
Antifolate drug resistance in P. falciparum is mediated by a combination of de novo folate cofactor synthesis and the uptake and utilization of intact exogenous folates.

Cite This Study

Milhous et al. (1985) studied this question.

synapsesocial.com/papers/6a717456a528af2d65c4160d https://doi.org/10.1128/aac.27.4.525

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April 1, 1985Antimicrobial Agents and Chemotherapy

In vitro activities of and mechanisms of resistance to antifol antimalarial drugs

View Full Paper

Ask AI

Bookmark

Authors

WMWilbur K. MilhousUniversity of Geneva NWNorman F. WeatherlyUniversity of North Carolina at Chapel Hill JBJean H. BowdreUniversity of North Carolina Hospitals

Discussion

Member takes

Implication

In vitro study reveals that exogenous folates antagonize antifol antimalarials in Plasmodium falciparum, indicating complex mechanisms underlying drug resistance.

Key Points

To establish reliable in vitro susceptibility testing methods and evaluate folate utilization and antifolate drug resistance mechanisms in Plasmodium falciparum.
Cultured four isolates of Plasmodium falciparum in standard medium as well as medium depleted of folic acid and p-aminobenzoic acid (PABA).
Assessed the in vitro antimalarial activity of sulfonamides and dihydrofolate reductase inhibitors in the presence and absence of exogenous folates and PABA.
Three of four P. falciparum isolates were successfully propagated and maintained in culture medium depleted of both folic acid and PABA.
The antimalarial potency of sulfonamides and dihydrofolate reductase inhibitors was variably antagonized by the addition of folic acid and PABA to the medium.
Antifolate drug resistance in P. falciparum is mediated by a combination of de novo folate cofactor synthesis and the uptake and utilization of intact exogenous folates.

Cite This Study

Milhous et al. (1985) studied this question.

synapsesocial.com/papers/6a717456a528af2d65c4160d https://doi.org/10.1128/aac.27.4.525

Also Consider

Synapse has enriched 2 closely related papers on similar clinical questions. Consider them for comparative context:

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