The mechanism of resistance to sulfa drugs in Plasmodium falciparum.

The sulfonamide and sulfone (sulfa) group of antimalarials has been used extensively throughout malaria endemic regions of the world to control this important infectious disease of humans. Sulfadoxine is the most extensively used drug of this group of drugs and is usually combined with pyrimethamine (Fansidar), particularly for the control of Plasmodium falciparum, the causative agent of the most lethal form of malaria. Resistance to the sulfadoxine/pyrimethamine combination is widespread. Analysis using molecular, genetic and biochemical approaches has shown that the mechanism of resistance to sulfadoxine involves mutation of dihydropteroate synthase, the enzyme target of this group of drugs. Understanding the mechanism of resistance of P. falciparum to sulfa drugs has allowed detailed analysis of the epidemiology of the spread of drug resistance alleles in the field(1)and, in the future, opens the way to the development of novel antimalarials to this target enzyme. Copyright 1999 Harcourt Publishers Ltd.

[1]  R. D. Walter,et al.  Biosynthesis of Folic Acid Compounds in Plasmodia. Purification and Properties of the 7,8-Dihydropteroate-Synthesizing Enzyme from Plasmodium chabaudi , 2009, Hoppe-Seyler's Zeitschrift fur physiologische Chemie.

[2]  J. E. Hyde,et al.  Allelic exchange at the endogenous genomic locus in Plasmodium falciparum proves the role of dihydropteroate synthase in sulfadoxine‐resistant malaria , 1998, The EMBO journal.

[3]  T. Triglia,et al.  Mutations in dihydropteroate synthase are responsible for sulfone and sulfonamide resistance in Plasmodium falciparum. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[4]  L. Hall,et al.  Mechanism of sulfonamide resistance in clinical isolates of Streptococcus pneumoniae , 1997, Antimicrobial agents and chemotherapy.

[5]  J. Champness,et al.  Crystal structure of the anti-bacterial sulfonamide drug target dihydropteroate synthase , 1997, Nature Structural Biology.

[6]  M. Page,et al.  Structure and function of the dihydropteroate synthase from Staphylococcus aureus. , 1997, Journal of molecular biology.

[7]  J. E. Hyde,et al.  Sulfadoxine resistance in the human malaria parasite Plasmodium falciparum is determined by mutations in dihydropteroate synthetase and an additional factor associated with folate utilization , 1997, Molecular microbiology.

[8]  W. Sirawaraporn,et al.  Antifolate-resistant mutants of Plasmodium falciparum dihydrofolate reductase. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[9]  A. Cowman,et al.  Characterization of promoters and stable transfection by homologous and nonhomologous recombination in Plasmodium falciparum. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Steketee,et al.  Rates and risk factors for mortality during the first two years of life in rural Malawi. , 1996, The American journal of tropical medicine and hygiene.

[11]  T. Wellems,et al.  Transformation of Plasmodium falciparum malaria parasites by homologous integration of plasmids that confer resistance to pyrimethamine. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[12]  O. Sköld,et al.  Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species , 1995, Journal of bacteriology.

[13]  J. E. Hyde,et al.  Sequence variation of the hydroxymethyldihydropterin pyrophosphokinase: dihydropteroate synthase gene in lines of the human malaria parasite, Plasmodium falciparum, with differing resistance to sulfadoxine. , 1994, European journal of biochemistry.

[14]  T. Triglia,et al.  Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[15]  W. Wernsdorfer,et al.  Plasmodium falciparum: susceptibility in vitro and in vivo to chloroquine and sulfadoxine-pyrimethamine in Ghanaian schoolchildren. , 1994, Transactions of the Royal Society of Tropical Medicine and Hygiene.

[16]  Y. Zhang,et al.  Inhibition of Plasmodium falciparum dihydropteroate synthetase and growth in vitro by sulfa drugs , 1991, Antimicrobial Agents and Chemotherapy.

[17]  M. van der Ploeg,et al.  DNA synthesis in Plasmodium berghei during asexual and sexual development. , 1986, Molecular and biochemical parasitology.

[18]  J. Inselburg,et al.  Plasmodium falciparum: induction, selection, and characterization of pyrimethamine-resistant mutants. , 1986, Experimental parasitology.

[19]  A. Jung,et al.  Mechanisms of sulfadoxine resistance in Plasmodium falciparum. , 1986, Molecular and biochemical parasitology.

[20]  J. Krungkrai,et al.  Guanosine triphosphate cyclohydrolase in Plasmodium falciparum and other Plasmodium species. , 1985, Molecular and biochemical parasitology.

[21]  W. Peters.  The problem of drug resistance in malaria , 1985, Parasitology.

[22]  R. Reese,et al.  Protein and nucleic acid synthesis during synchronized growth of Plasmodium falciparum , 1984, Journal of bacteriology.

[23]  C. Brockelman,et al.  Cross resistance of pyrimethamine and sulfadoxine to their related compounds in Plasmodium falciparum. , 1984, Southeast Asian Journal of Tropical Medicine and Public Health.

[24]  I. Sherman,et al.  Biochemistry of Plasmodium (malarial parasites). , 1979, Microbiological reviews.

[25]  R. Ferone.  The enzymic synthesis of dihydropteroate and dihydrofolate by Plasmodium berghei. , 1973, The Journal of protozoology.

[26]  C. Canfield,et al.  Plasmodium knowlesi: in vitro evaluation of antimalarial activity of folic acid inhibitors. , 1971, Experimental parasitology.

[27]  W. Gutteridge,et al.  Action of pyrimethamine and related drugs against Plasmodium knowlesi in vitro , 1971, Parasitology.

[28]  G. Coatney,et al.  The influence of antimalarial drugs on nucleic acid synthesis in Plasmodium gallinaceum and Plasmodium berghei. , 1961, Biochemical pharmacology.

[29]  I. Rollo.  The mode of action of sulphonamides, proguanil and pyrimethamine on Plasmodium gallinaceum. , 1955, British journal of pharmacology and chemotherapy.

[30]  A. K. Miller.  Folic Acid and Biotin Synthesis by Sulfonamide-sensitive and Sulfonamide-resistant Strains of Escherichia coli. , 1944 .

[31]  D. D. Woods.  The Relation of p-aminobenzoic Acid to the Mechanism of the Action of Sulphanilamide. , 1940 .

[32]  O. Doumbo,et al.  P. falciparum dihydrofolate reductase and dihydropteroate synthase mutations: epidemiology and role in clinical resistance to antifolates. , 1998, Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy.

[33]  B. Nichols,et al.  Characterization of a mutationally altered dihydropteroate synthase contributing to sulfathiazole resistance in Escherichia coli. , 1998, Microbial drug resistance.

[34]  J. Krungkrai,et al.  De novo and salvage biosynthesis of pteroylpentaglutamates in the human malaria parasite, Plasmodium falciparum. , 1989, Molecular and biochemical parasitology.

[35]  W. Watkins,et al.  Antagonism of sulfadoxine and pyrimethamine antimalarial activity in vitro by p-aminobenzoic acid, p-aminobenzoylglutamic acid and folic acid. , 1985, Molecular and biochemical parasitology.

[36]  J. Inselburg,et al.  Synthesis of DNA during the asexual cycle of Plasmodium falciparum in culture. , 1984, Molecular and biochemical parasitology.

[37]  W. Peters,et al.  Antimalarial drugs. II. Current antimalarials and new drug developments. , 1984 .

[38]  R. Leimer,et al.  Sulphonamides and Sulphones , 1984 .

[39]  W. Watkins,et al.  The activity of proguanil and its metabolites, cycloguanil and p-chlorophenylbiguanide, against Plasmodium falciparum in vitro. , 1984, Annals of tropical medicine and parasitology.

[40]  C. Newbold,et al.  Stage specific protein and nucleic acid synthesis during the asexual cycle of the rodent malaria Plasmodium chabaudi. , 1982, Molecular and biochemical parasitology.

[41]  R. D. Walter,et al.  7,8-Dihydropteroate-synthesizing enzyme from Plasmodium chabaudi. , 1980, Methods in enzymology.

[42]  W. Wernsdorfer,et al.  The importance of malaria in the world. , 1980 .

[43]  R. Ferone,et al.  Folate metabolism in malaria. , 1977, Bulletin of the World Health Organization.

[44]  J. McCullough,et al.  Dihydropteroate synthetase from Plasmodium berghei: isolation, properties, and inhibition by dapsone and sulfadiazine. , 1974, Molecular pharmacology.