dihydropteroate synthase

Summary

Summary: An enzyme that catalyzes the formation of dihydropteroate from p-aminobenzoic acid and dihydropteridine-hydroxymethyl-pyrophosphate. EC 2.5.1.15.

Top Publications

  1. Curtis J, Duraisingh M, Warhurst D. In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment. J Infect Dis. 1998;177:1429-33 pubmed
  2. Bertin G, Briand V, Bonaventure D, Carrieu A, Massougbodji A, Cot M, et al. Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin. Malar J. 2011;10:196 pubmed publisher
    ..Molecular markers have been recommended to monitor SP efficacy for IPTp, but given the current prevalence of mutant parasites their usefulness is questionable. ..
  3. Zakeri S, Afsharpad M, Raeisi A, Djadid N. Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran. Malar J. 2007;6:148 pubmed
    ..Finding the fixed level of CQ resistance polymorphisms (pfcrt 76T) suggests that CQ must be withdrawn from the current treatment strategy in Iran, while SP may remain the treatment of choice for uncomplicated malaria. ..
  4. Levin I, Mevarech M, Palfey B. Characterization of a novel bifunctional dihydropteroate synthase/dihydropteroate reductase enzyme from Helicobacter pylori. J Bacteriol. 2007;189:4062-9 pubmed
    ..Previous studies demonstrated that the H. pylori dihydropteroate synthase gene folP can complement an Escherichia coli strain in which folA and folM, encoding two distinct DHFRs, ..
  5. Kuesap J, Rungsrihirunrat K, Thongdee P, Ruangweerayut R, Na Bangchang K. Change in mutation patterns of Plasmodium vivax dihydrofolate reductase (Pvdhfr) and dihydropteroate synthase (Pvdhps) in P. vivax isolates from malaria endemic areas of Thailand. Mem Inst Oswaldo Cruz. 2011;106 Suppl 1:130-3 pubmed
    ..vivax dihydrofolate reductase (Pvdhfr) and P. vivax dihydropteroate synthase (Pvdhps) in 103 blood samples collected from patients with P...
  6. Naidoo I, Roper C. Drug resistance maps to guide intermittent preventive treatment of malaria in African infants. Parasitology. 2011;138:1469-79 pubmed publisher
    ..There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi. ..
  7. Helweg Larsen J, Benfield T, Eugen Olsen J, Lundgren J, Lundgren B. Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia. Lancet. 1999;354:1347-51 pubmed
    ..Sulpha resistance in many microorganisms is caused by point mutations in dihydropteroate synthase (DHPS), an enzyme that is essential for folate biosynthesis...
  8. Corredor V, Murillo C, Echeverry D, Benavides J, Pearce R, Roper C, et al. Origin and dissemination across the Colombian Andes mountain range of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum. Antimicrob Agents Chemother. 2010;54:3121-5 pubmed publisher
  9. Dini L, du Plessis M, Frean J, Fernandez V. High prevalence of dihydropteroate synthase mutations in Pneumocystis jirovecii isolated from patients with Pneumocystis pneumonia in South Africa. J Clin Microbiol. 2010;48:2016-21 pubmed publisher
    ..Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of ..
  10. Crothers K, Huang L, Morris A, Fox M, Groner G, Turner J, et al. Pneumocystis dihydropteroate synthase mutations in patients with Pneumocystis pneumonia who are newly diagnosed with HIV infection. J Eukaryot Microbiol. 2003;50 Suppl:609-10 pubmed

Detail Information

Publications62

  1. Curtis J, Duraisingh M, Warhurst D. In vivo selection for a specific genotype of dihydropteroate synthetase of Plasmodium falciparum by pyrimethamine-sulfadoxine but not chlorproguanil-dapsone treatment. J Infect Dis. 1998;177:1429-33 pubmed
  2. Bertin G, Briand V, Bonaventure D, Carrieu A, Massougbodji A, Cot M, et al. Molecular markers of resistance to sulphadoxine-pyrimethamine during intermittent preventive treatment of pregnant women in Benin. Malar J. 2011;10:196 pubmed publisher
    ..Molecular markers have been recommended to monitor SP efficacy for IPTp, but given the current prevalence of mutant parasites their usefulness is questionable. ..
  3. Zakeri S, Afsharpad M, Raeisi A, Djadid N. Prevalence of mutations associated with antimalarial drugs in Plasmodium falciparum isolates prior to the introduction of sulphadoxine-pyrimethamine as first-line treatment in Iran. Malar J. 2007;6:148 pubmed
    ..Finding the fixed level of CQ resistance polymorphisms (pfcrt 76T) suggests that CQ must be withdrawn from the current treatment strategy in Iran, while SP may remain the treatment of choice for uncomplicated malaria. ..
  4. Levin I, Mevarech M, Palfey B. Characterization of a novel bifunctional dihydropteroate synthase/dihydropteroate reductase enzyme from Helicobacter pylori. J Bacteriol. 2007;189:4062-9 pubmed
    ..Previous studies demonstrated that the H. pylori dihydropteroate synthase gene folP can complement an Escherichia coli strain in which folA and folM, encoding two distinct DHFRs, ..
  5. Kuesap J, Rungsrihirunrat K, Thongdee P, Ruangweerayut R, Na Bangchang K. Change in mutation patterns of Plasmodium vivax dihydrofolate reductase (Pvdhfr) and dihydropteroate synthase (Pvdhps) in P. vivax isolates from malaria endemic areas of Thailand. Mem Inst Oswaldo Cruz. 2011;106 Suppl 1:130-3 pubmed
    ..vivax dihydrofolate reductase (Pvdhfr) and P. vivax dihydropteroate synthase (Pvdhps) in 103 blood samples collected from patients with P...
  6. Naidoo I, Roper C. Drug resistance maps to guide intermittent preventive treatment of malaria in African infants. Parasitology. 2011;138:1469-79 pubmed publisher
    ..There are clear deficiencies in molecular surveillance data coverage. We discuss requirements for ongoing surveillance of SP resistance markers in support of the use of SP-IPTi. ..
  7. Helweg Larsen J, Benfield T, Eugen Olsen J, Lundgren J, Lundgren B. Effects of mutations in Pneumocystis carinii dihydropteroate synthase gene on outcome of AIDS-associated P. carinii pneumonia. Lancet. 1999;354:1347-51 pubmed
    ..Sulpha resistance in many microorganisms is caused by point mutations in dihydropteroate synthase (DHPS), an enzyme that is essential for folate biosynthesis...
  8. Corredor V, Murillo C, Echeverry D, Benavides J, Pearce R, Roper C, et al. Origin and dissemination across the Colombian Andes mountain range of sulfadoxine-pyrimethamine resistance in Plasmodium falciparum. Antimicrob Agents Chemother. 2010;54:3121-5 pubmed publisher
  9. Dini L, du Plessis M, Frean J, Fernandez V. High prevalence of dihydropteroate synthase mutations in Pneumocystis jirovecii isolated from patients with Pneumocystis pneumonia in South Africa. J Clin Microbiol. 2010;48:2016-21 pubmed publisher
    ..Mutations in the P. jirovecii fas gene, which encodes dihydropteroate synthase (DHPS), are associated with prior exposure to sulfa drugs, and their appearance suggests the emergence of ..
  10. Crothers K, Huang L, Morris A, Fox M, Groner G, Turner J, et al. Pneumocystis dihydropteroate synthase mutations in patients with Pneumocystis pneumonia who are newly diagnosed with HIV infection. J Eukaryot Microbiol. 2003;50 Suppl:609-10 pubmed
  11. Contreras C, Cortese J, Caraballo A, Plowe C. Genetics of drug-resistant Plasmodium falciparum malaria in the Venezuelan state of Bolivar. Am J Trop Med Hyg. 2002;67:400-5 pubmed
    ..Two dihydropteroate synthase (dhps) mutations also involved in SP resistance, A581G and K540E, were detected in 90% and 67% of the ..
  12. Zar H, Alvarez Martinez M, Harrison A, Meshnick S. Prevalence of dihydropteroate synthase mutants in HIV-infected South African children with Pneumocystis jiroveci pneumonia. Clin Infect Dis. 2004;39:1047-51 pubmed
    ..virus (HIV)-infected infants in Africa, but the prevalence of mutations in the gene encoding dihydropteroate synthase (DHPS) in isolates from Africa has not been reported...
  13. Alifrangis M, Enosse S, Khalil I, Tarimo D, Lemnge M, Thompson R, et al. Prediction of Plasmodium falciparum resistance to sulfadoxine/pyrimethamine in vivo by mutations in the dihydrofolate reductase and dihydropteroate synthetase genes: a comparative study between sites of differing endemicity. Am J Trop Med Hyg. 2003;69:601-6 pubmed
  14. Alifrangis M, Lemnge M, Rønn A, Segeja M, Magesa S, Khalil I, et al. Increasing prevalence of wildtypes in the dihydrofolate reductase gene of Plasmodium falciparum in an area with high levels of sulfadoxine/pyrimethamine resistance after introduction of treated bed nets. Am J Trop Med Hyg. 2003;69:238-43 pubmed
    ..The impact of ITNs on the transmission intensity seems not only to affect the overall malaria morbidity, but may even facilitate restoration of susceptibility to antimalarial drugs. ..
  15. Wernsdorfer W, Noedl H. Molecular markers for drug resistance in malaria: use in treatment, diagnosis and epidemiology. Curr Opin Infect Dis. 2003;16:553-8 pubmed
    ..of a combined Plasmodium falciparum dihydrofolate reductase gene, pfdhfr, 59ARG and Plasmodium falciparum dihydropteroate synthase gene, pfdhps, 540GLU marker in reliably representing resistance to antifolates...
  16. Nahimana A, Rabodonirina M, Helweg Larsen J, Meneau I, Francioli P, Bille J, et al. Sulfa resistance and dihydropteroate synthase mutants in recurrent Pneumocystis carinii pneumonia. Emerg Infect Dis. 2003;9:864-7 pubmed
    ..of sulfa or sulfone prophylaxis is associated with mutations in Pneumocystis carinii gene coding for dihydropteroate synthase (DHPS). The DHPS genotype was analyzed in AIDS patients who had two separate episodes of P...
  17. Mouillon J, Ravanel S, Douce R, Rebeille F. Folate synthesis in higher-plant mitochondria: coupling between the dihydropterin pyrophosphokinase and the dihydropteroate synthase activities. Biochem J. 2002;363:313-9 pubmed
    The plant enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase (HPPK/DHPS) is a mitochondrial bifunctional protein involved in tetrahydrofolate synthesis...
  18. Iliades P, Meshnick S, Macreadie I. Mutations in the Pneumocystis jirovecii DHPS gene confer cross-resistance to sulfa drugs. Antimicrob Agents Chemother. 2005;49:741-8 pubmed
    ..failure and sulfa drug resistance have been implicated epidemiologically with point mutations in dihydropteroate synthase (DHPS) of P. jirovecii. P...
  19. Baca A, Sirawaraporn R, Turley S, Sirawaraporn W, Hol W. Crystal structure of Mycobacterium tuberculosis 7,8-dihydropteroate synthase in complex with pterin monophosphate: new insight into the enzymatic mechanism and sulfa-drug action. J Mol Biol. 2000;302:1193-212 pubmed
    The enzyme 7,8-dihydropteroate synthase (DHPS) catalyzes the condensation of para-aminobenzoic acid (pABA) with 6-hydroxymethyl-7, 8-dihydropterin-pyrophosphate to form 7,8-dihydropteroate and pyrophosphate...
  20. Sridaran S, McClintock S, Syphard L, Herman K, Barnwell J, Udhayakumar V. Anti-folate drug resistance in Africa: meta-analysis of reported dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) mutant genotype frequencies in African Plasmodium falciparum parasite populations. Malar J. 2010;9:247 pubmed publisher
    Mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes of Plasmodium falciparum are associated with resistance to anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP)...
  21. Pemble C, Mehta P, Mehra S, Li Z, Nourse A, Lee R, et al. Crystal structure of the 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase•dihydropteroate synthase bifunctional enzyme from Francisella tularensis. PLoS ONE. 2010;5:e14165 pubmed publisher
    The 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) and dihydropteroate synthase (DHPS) enzymes catalyze sequential metabolic reactions in the folate biosynthetic pathway of bacteria and lower eukaryotes...
  22. Swedberg G, Ringertz S, Sk ld O. Sulfonamide resistance in Streptococcus pyogenes is associated with differences in the amino acid sequence of its chromosomal dihydropteroate synthase. Antimicrob Agents Chemother. 1998;42:1062-7 pubmed
    ..of Streptococcus pyogenes was found to be associated with alterations of the chromosomally encoded dihydropteroate synthase (DHPS). There were 111 different nucleotides (13...
  23. Bwijo B, Kaneko A, Takechi M, Zungu I, Moriyama Y, Lum J, et al. High prevalence of quintuple mutant dhps/dhfr genes in Plasmodium falciparum infections seven years after introduction of sulfadoxine and pyrimethamine as first line treatment in Malawi. Acta Trop. 2003;85:363-73 pubmed
    ..Seven years after this change, we investigated the prevalence of dihydropteroate synthase (dhps) and dihydrofolate reductase (dhfr) mutations, known to be associated with decreased sensitivity to ..
  24. Djaman J, Mazabraud A, Basco L. Sulfadoxine-pyrimethamine susceptibilities and analysis of the dihydrofolate reductase and dihydropteroate synthase of Plasmodium falciparum isolates from Côte d'Ivoire. Ann Trop Med Parasitol. 2007;101:103-12 pubmed
    ..04). Resistance to SP appears to be an increasing problem in southern Côte d'Ivoire and one which may now justify a change away from this drug combination as the first- or second-line treatment for P. falciparum malaria in this area. ..
  25. Kyabayinze D, Cattamanchi A, Kamya M, Rosenthal P, Dorsey G. Validation of a simplified method for using molecular markers to predict sulfadoxine-pyrimethamine treatment failure in African children with falciparum malaria. Am J Trop Med Hyg. 2003;69:247-52 pubmed
    ..7, P = 0.009). These results support a previously proposed method of predicting clinical outcomes based on the prevalence of these two mutations. ..
  26. Latouche S, Lacube P, Maury E, Bolognini J, Develoux M, Girard P, et al. Pneumocystis jirovecii dihydropteroate synthase genotypes in French patients with pneumocystosis: a 1998-2001 prospective study. Med Mycol. 2003;41:533-7 pubmed
    b>Dihydropteroate synthase gene (DHPS) mutations at codons 55 and 57 have been associated with sulfa/sulfone resistance in Pneumocystis jirovecii strains from patients who previously received prophylaxis...
  27. Mendez F, Munoz A, Carrasquilla G, Jurado D, Arevalo Herrera M, Cortese J, et al. Determinants of treatment response to sulfadoxine-pyrimethamine and subsequent transmission potential in falciparum malaria. Am J Epidemiol. 2002;156:230-8 pubmed
    ..Exposures of interest were mutations in Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthase that confer resistance to pyrimethamine and sulfadoxine, respectively...
  28. Hawkins V, Joshi H, Rungsihirunrat K, Na Bangchang K, Sibley C. Antifolates can have a role in the treatment of Plasmodium vivax. Trends Parasitol. 2007;23:213-22 pubmed
    ..Mutations in the genes that encode dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) confer resistance to pyrimethamine and sulfadoxine, respectively...
  29. Hayton K, Su X. Genetic and biochemical aspects of drug resistance in malaria parasites. Curr Drug Targets Infect Disord. 2004;4:1-10 pubmed
    ..efforts are highlighted by the demonstration of mutations in the parasite dihydrofolate reductase and dihydropteroate synthase genes conferring resistance to pyrimethamine and sulfadoxine, respectively, and by the recent discovery ..
  30. Menegon M, Majori G, Severini C. Genetic variations of the Plasmodium vivax dihydropteroate synthase gene. Acta Trop. 2006;98:196-9 pubmed
    b>Dihydropteroate synthase gene of Plasmodium vivax was recently identified. In the present study, the sequences of the dyhydropteroate synthase gene of 68 P. vivax isolates from various geographic areas were compared...
  31. Alvarez Martinez M, Moreno A, Miro J, Valls M, Rivas P, de Lazzari E, et al. Pneumocystis jirovecii pneumonia in Spanish HIV-infected patients in the combined antiretroviral therapy era: prevalence of dihydropteroate synthase mutations and prognostic factors of mortality. Diagn Microbiol Infect Dis. 2008;62:34-43 pubmed publisher
    ..The influence of P. jirovecii dihydropteroate synthase (DHPS) gene mutations on survival is controversial and has not been reported in Spain...
  32. Enosse S, Magnussen P, Abacassamo F, Gómez Olivé X, Rønn A, Thompson R, et al. Rapid increase of Plasmodium falciparum dhfr/dhps resistant haplotypes, after the adoption of sulphadoxine-pyrimethamine as first line treatment in 2002, in southern Mozambique. Malar J. 2008;7:115 pubmed publisher
    ..falciparum populations and may even endanger the sensitivity to the second-line drug, Coartem. ..
  33. Omar S, Mens P, Schoone G, Yusuf A, Mwangi J, Kaniaru S, et al. Plasmodium falciparum: evaluation of a quantitative nucleic acid sequence-based amplification assay to predict the outcome of sulfadoxine-pyrimethamine treatment of uncomplicated malaria. Exp Parasitol. 2005;110:73-9 pubmed
    ..5% (95% CI = 13.0-38.0). The analysis of a day 7 blood sample with QT-NASBA allows for the prediction of late clinical or parasitological treatment failure in the majority of the cases analysed in the present study. ..
  34. Talisuna A, Nalunkuma Kazibwe A, Langi P, Mutabingwa T, Watkins W, Van Marck E, et al. Two mutations in dihydrofolate reductase combined with one in the dihydropteroate synthase gene predict sulphadoxine-pyrimethamine parasitological failure in Ugandan children with uncomplicated falciparum malaria. Infect Genet Evol. 2004;4:321-7 pubmed
    The point mutations in the Plasmodium falciparum dihydrofolate reductase (dhfr) and the dihydropteroate synthase (dhps) genes that are linked to sulphadoxine-pyrimethamine (SP) resistance in vitro have been well characterised...
  35. Iliades P, Meshnick S, Macreadie I. Dihydropteroate synthase mutations in Pneumocystis jiroveci can affect sulfamethoxazole resistance in a Saccharomyces cerevisiae model. Antimicrob Agents Chemother. 2004;48:2617-23 pubmed
    b>Dihydropteroate synthase (DHPS) mutations in Pneumocystis jiroveci have been associated epidemiologically with resistance to sulfamethoxazole (SMX). Since P. jiroveci cannot be cultured, inherent drug resistance cannot be measured...
  36. Totet A, Latouche S, Lacube P, Pautard J, Jounieaux V, Raccurt C, et al. Pneumocystis jirovecii dihydropteroate synthase genotypes in immunocompetent infants and immunosuppressed adults, Amiens, France. Emerg Infect Dis. 2004;10:667-73 pubmed
    To date, investigations of Pneumocystis jirovecii circulation in the human reservoir through the dihydropteroate synthase (DHPS) locus analysis have only been conducted by examining P...
  37. Stammers D, Achari A, Somers D, Bryant P, Rosemond J, Scott D, et al. 2.0 A X-ray structure of the ternary complex of 7,8-dihydro-6-hydroxymethylpterinpyrophosphokinase from Escherichia coli with ATP and a substrate analogue. FEBS Lett. 1999;456:49-53 pubmed
  38. Garg S, Saxena V, Lumb V, Pakalapati D, Boopathi P, Subudhi A, et al. Novel mutations in the antifolate drug resistance marker genes among Plasmodium vivax isolates exhibiting severe manifestations. Exp Parasitol. 2012;132:410-6 pubmed publisher
    ..However, the presence of novel mutations in the PvDHPS gene indicate a degree of polymorphism of this molecule which is in contrast to available published information...
  39. Qvarnstr m Y, Swedberg G. Sulphonamide resistant commensal Neisseria with alterations in the dihydropteroate synthase can be isolated from carriers not exposed to sulphonamides. BMC Microbiol. 2002;2:34 pubmed
    ..clones were identified and the resistance phenotype could be explained by amino acid variations in their dihydropteroate synthase, the target molecule for sulphonamides...
  40. Bouyou Akotet M, Mawili Mboumba D, Tchantchou T, Kombila M. High prevalence of sulfadoxine/pyrimethamine-resistant alleles of Plasmodium falciparum isolates in pregnant women at the time of introduction of intermittent preventive treatment with sulfadoxine/pyrimethamine in Gabon. J Antimicrob Chemother. 2010;65:438-41 pubmed publisher
    ..The frequency of dhfr and dhps point mutations was assessed in Plasmodium falciparum isolates from pregnant women in Libreville...
  41. Nopponpunth V, Sirawaraporn W, Greene P, Santi D. Cloning and expression of Mycobacterium tuberculosis and Mycobacterium leprae dihydropteroate synthase in Escherichia coli. J Bacteriol. 1999;181:6814-21 pubmed
    The genes for dihydropteroate synthase of Mycobacterium tuberculosis and Mycobacterium leprae were isolated by hybridization with probes amplified from the genomic DNA libraries...
  42. Andriantsoanirina V, Ratsimbasoa A, Bouchier C, Jahevitra M, Rabearimanana S, Radrianjafy R, et al. Plasmodium falciparum drug resistance in Madagascar: facing the spread of unusual pfdhfr and pfmdr-1 haplotypes and the decrease of dihydroartemisinin susceptibility. Antimicrob Agents Chemother. 2009;53:4588-97 pubmed publisher
    ..In the context of the implementation of the new national policy for the fight against malaria, continued surveillance for the detection of P. falciparum resistance in the future is required. ..
  43. Schmider N, Peyerl Hoffmann G, Restrepo M, Jelinek T. Short communication: point mutations in the dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum isolates from Colombia. Trop Med Int Health. 2003;8:129-32 pubmed
    Point mutations in the dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) genes of Plasmodium falciparum can lead to an increasing resistance of P. falciparum to pyrimethamine/sulphadoxine...
  44. Visconti E, Ortona E, Mencarini P, Margutti P, Marinaci S, Zolfo M, et al. Mutations in dihydropteroate synthase gene of Pneumocystis carinii in HIV patients with Pneumocystis carinii pneumonia. Int J Antimicrob Agents. 2001;18:547-51 pubmed
    The purpose of this study was to determine whether dihydropteroate synthase gene (DHPS) mutations were associated with the failure of sulpha/sulphone drugs used as prophylaxis agents in HIV infected patients...
  45. Mbugi E, Mutayoba B, Malisa A, Balthazary S, Nyambo T, Mshinda H. Drug resistance to sulphadoxine-pyrimethamine in Plasmodium falciparum malaria in Mlimba, Tanzania. Malar J. 2006;5:94 pubmed
    ..The genes for dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) were used as markers, to investigate parasite resistance to SP in 141 children aged less than 5 ..
  46. Huang L, Crothers K, Atzori C, Benfield T, Miller R, Rabodonirina M, et al. Dihydropteroate synthase gene mutations in Pneumocystis and sulfa resistance. Emerg Infect Dis. 2004;10:1721-8 pubmed
    ..In other microorganisms, sulfa drug resistance has resulted from specific point mutations in the dihydropteroate synthase (DHPS) gene. Similar mutations have been observed in P. jirovecii...
  47. Khalil I, Alifrangis M, Rønn A, Gabar H, Jelinek T, Satti G, et al. Pyrimethamine/sulfadoxine combination in the treatment of uncomplicated falciparum malaria: relation between dihydropteroate synthase/dihydrofolate reductase genotypes, sulfadoxine plasma levels, and treatment outcome. Am J Trop Med Hyg. 2002;67:225-9 pubmed
    ..The findings suggest that the presence of Ile 51/Asn 108 dhfr mutations and Ala 436 dhps confers decreased susceptibility of P. falciparum to PYR/SDX in areas of low endemicity. ..
  48. Tahar R, Basco L. Molecular epidemiology of malaria in Cameroon. XXVII. Clinical and parasitological response to sulfadoxine-pyrimethamine treatment and Plasmodium falciparum dihydrofolate reductase and dihydropteroate synthase alleles in Cameroonian children. Acta Trop. 2007;103:81-9 pubmed
    ..response to sulfadoxine-pyrimethamine and allelic combinations of dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes...
  49. Jonsson M, Swedberg G. Hydroxymethyldihydropterin pyrophosphokinase from Plasmodium falciparum complements a folK-knockout mutant in E. coli when expressed as a separate polypeptide detached from dihydropteroate synthase. Mol Biochem Parasitol. 2005;140:123-5 pubmed
  50. Nzila A. Inhibitors of de novo folate enzymes in Plasmodium falciparum. Drug Discov Today. 2006;11:939-44 pubmed
    ..They are developed as synergistic combinations of inhibitors of dihydrofolate reductase (DHFR) and of dihydropteroate synthase (DHPS). DHPS inhibitors are sulfur-based drugs, analogs of sulfanilamide...
  51. Hevener K, Zhao W, Ball D, Babaoglu K, Qi J, White S, et al. Validation of molecular docking programs for virtual screening against dihydropteroate synthase. J Chem Inf Model. 2009;49:444-60 pubmed publisher
    b>Dihydropteroate synthase (DHPS) is the target of the sulfonamide class of antibiotics and has been a validated antibacterial drug target for nearly 70 years...
  52. Auliff A, Wilson D, Russell B, Gao Q, Chen N, Anh L, et al. Amino acid mutations in Plasmodium vivax DHFR and DHPS from several geographical regions and susceptibility to antifolate drugs. Am J Trop Med Hyg. 2006;75:617-21 pubmed
    ..Parasites with the S58R/S117N dhfr allelic type showed an MIC level for pyrimethamine and cycloguanil comparable to that previously reported, but were susceptible to WR99210. ..
  53. Mberu E, Nzila A, Nduati E, Ross A, Monks S, Kokwaro G, et al. Plasmodium falciparum: in vitro activity of sulfadoxine and dapsone in field isolates from Kenya: point mutations in dihydropteroate synthase may not be the only determinants in sulfa resistance. Exp Parasitol. 2002;101:90-6 pubmed
    We have determined the relationship between point mutations in the gene that encodes the sulfa target, dihydropteroate synthase (DHPS) and the chemosensitivity profile to sulfadoxine and dapsone in 67 isolates from Kilifi, Kenya...
  54. Zingale A, Carrera P, Lazzarin A, Scarpellini P. Detection of Pneumocystis carinii and characterization of mutations associated with sulfa resistance in bronchoalveolar lavage samples from human immunodeficiency virus-infected subjects. J Clin Microbiol. 2003;41:2709-12 pubmed
    ..Mutations were identified in 28 out of 70 (40%) PCR-positive specimens and were significantly more common in patients exposed to sulfa drugs (21 out of 29 [72.4%]) than in those not exposed to sulfa drugs (4 out of 35 [11.4%])...
  55. Gebru Woldearegai T, Hailu A, Grobusch M, Kun J. Molecular surveillance of mutations in dihydrofolate reductase and dihydropteroate synthase genes of Plasmodium falciparum in Ethiopia. Am J Trop Med Hyg. 2005;73:1131-4 pubmed
    Point mutations in the genes for dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) of Plasmodium falciparum isolates are associated with sulfadoxine/pyrimethamine (SP) treatment failure, respectively...
  56. Rebeille F, Macherel D, Mouillon J, Garin J, Douce R. Folate biosynthesis in higher plants: purification and molecular cloning of a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase localized in mitochondria. EMBO J. 1997;16:947-57 pubmed
    ..This reaction is catalyzed by a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase enzyme, which represented 0.04-0.06% of the matrix proteins. The enzyme had a native mol...
  57. Aspinall T, Joynson D, Guy E, Hyde J, Sims P. The molecular basis of sulfonamide resistance in Toxoplasma gondii and implications for the clinical management of toxoplasmosis. J Infect Dis. 2002;185:1637-43 pubmed
    Polymerase chain reaction amplification and DNA sequencing of the Toxoplasma gondii dihydropteroate synthase gene (dhps) identified 4 alleles among parasite populations from 32 cases of human toxoplasmosis...
  58. Barnadas C, Tichit M, Bouchier C, Ratsimbasoa A, Randrianasolo L, Raherinjafy R, et al. Plasmodium vivax dhfr and dhps mutations in isolates from Madagascar and therapeutic response to sulphadoxine-pyrimethamine. Malar J. 2008;7:35 pubmed publisher
  59. Jelinek T, Peyerl Hoffmann G, Mühlberger N, Wichmann O, Wilhelm M, Schmider N, et al. Molecular surveillance of drug resistance through imported isolates of Plasmodium falciparum in Europe. Malar J. 2002;1:11 pubmed
    ..The screening results were used to map the prevalence of mutations and, thus, levels of potential drug resistance in endemic areas world-wide...
  60. Rungsihirunrat K, Sibley C, Mungthin M, Na Bangchang K. Geographical distribution of amino acid mutations in Plasmodium vivax DHFR and DHPS from malaria endemic areas of Thailand. Am J Trop Med Hyg. 2008;78:462-7 pubmed
    Both malaria treatment and prophylaxis target the parasite dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) enzymes...
  61. Alam M, de Souza D, Vinayak S, Griffing S, Poe A, Duah N, et al. Selective sweeps and genetic lineages of Plasmodium falciparum drug -resistant alleles in Ghana. J Infect Dis. 2011;203:220-7 pubmed publisher
    ..Because of the possible role of pfmdr1 in amodiaquine and mefloquine resistance, demonstrating selection on pfmdr1 and defining lineages of resistant alleles in an African population holds great importance. ..
  62. Padayachee T, Klugman K. Novel expansions of the gene encoding dihydropteroate synthase in trimethoprim-sulfamethoxazole-resistant Streptococcus pneumoniae. Antimicrob Agents Chemother. 1999;43:2225-30 pubmed
    ..clinical isolates of Streptococcus pneumoniae revealed chromosomal mutations within the gene encoding dihydropteroate synthase that play a role in conferring resistance to sulfamethoxazole...