The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics
Abstract Background The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. Objective To inves...
Published in: | Malaria Journal |
---|---|
Main Authors: | , , , , , , |
Format: | Article in Journal/Newspaper |
Language: | English |
Published: |
BMC
2007
|
Subjects: | |
Online Access: | https://doi.org/10.1186/1475-2875-6-108 https://doaj.org/article/980574e5a017419c9a6b27faeab8f416 |
id |
ftdoajarticles:oai:doaj.org/article:980574e5a017419c9a6b27faeab8f416 |
---|---|
record_format |
openpolar |
spelling |
ftdoajarticles:oai:doaj.org/article:980574e5a017419c9a6b27faeab8f416 2023-05-15T15:10:03+02:00 The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics Elbashir Mustafa I Masuadi Emad M Bygbjerg Ib C Khalil Insaf F Alifrangis Michael A-Elbasit Ishraga E Giha Hayder A 2007-08-01T00:00:00Z https://doi.org/10.1186/1475-2875-6-108 https://doaj.org/article/980574e5a017419c9a6b27faeab8f416 EN eng BMC http://www.malariajournal.com/content/6/1/108 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-6-108 1475-2875 https://doaj.org/article/980574e5a017419c9a6b27faeab8f416 Malaria Journal, Vol 6, Iss 1, p 108 (2007) Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 article 2007 ftdoajarticles https://doi.org/10.1186/1475-2875-6-108 2022-12-31T12:33:26Z Abstract Background The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. Objective To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. Method Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA. Results & conclusion Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Malaria Journal 6 1 108 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
spellingShingle |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 Elbashir Mustafa I Masuadi Emad M Bygbjerg Ib C Khalil Insaf F Alifrangis Michael A-Elbasit Ishraga E Giha Hayder A The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Infectious and parasitic diseases RC109-216 |
description |
Abstract Background The Plasmodium falciparum dihydrofolate reductase (DHFR) and dihydropteroate synthetase (DHPS) are enzymes of central importance in parasite metabolism. The dhfr and dhps gene mutations are known to be associated with sulphadoxine/pyrimethamine (SP) resistance. Objective To investigate the effects of dhfr/dhps mutations on parasite characteristics other than SP resistance. Method Parasite infections obtained from 153 Sudanese patients with uncomplicated falciparum malaria treated with SP or SP + chloroquine, were successfully genotyped at nine codons in the dhfr/dhps genes by PCR-ELISA. Results & conclusion Mutations were detected in dhfr at N51I, S108N and C59R, and in at dhps at A/S436F, A437G, K540E and A581G, the maximum number of mutations per infection were five. Based on number of mutant codons per infection (multiplicity of mutation, MOM), the infections were organized into six grades: wild-types (grade 0; frequency, 0.03) and infections with MOM grades of 1 to 5, with the following cumulative frequency; 0.97, 0.931, 0.866, 0.719, 0.121, respectively. There was no significant association between the MOM and SP response. Importantly, immunity, using age as a surrogate marker, contributed significantly to the clearance of parasites with multiple dhfr/dhps mutations. However, these mutations have a survival advantage as they were associated with increased gametocytogenesis. The above implications of dhfr/dhps mutations were associated with MOM 2 to 5, regardless of the gene/codon locus. |
format |
Article in Journal/Newspaper |
author |
Elbashir Mustafa I Masuadi Emad M Bygbjerg Ib C Khalil Insaf F Alifrangis Michael A-Elbasit Ishraga E Giha Hayder A |
author_facet |
Elbashir Mustafa I Masuadi Emad M Bygbjerg Ib C Khalil Insaf F Alifrangis Michael A-Elbasit Ishraga E Giha Hayder A |
author_sort |
Elbashir Mustafa I |
title |
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics |
title_short |
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics |
title_full |
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics |
title_fullStr |
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics |
title_full_unstemmed |
The implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of Plasmodium falciparum characteristics |
title_sort |
implication of dihydrofolate reductase and dihydropteroate synthetase gene mutations in modification of plasmodium falciparum characteristics |
publisher |
BMC |
publishDate |
2007 |
url |
https://doi.org/10.1186/1475-2875-6-108 https://doaj.org/article/980574e5a017419c9a6b27faeab8f416 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Malaria Journal, Vol 6, Iss 1, p 108 (2007) |
op_relation |
http://www.malariajournal.com/content/6/1/108 https://doaj.org/toc/1475-2875 doi:10.1186/1475-2875-6-108 1475-2875 https://doaj.org/article/980574e5a017419c9a6b27faeab8f416 |
op_doi |
https://doi.org/10.1186/1475-2875-6-108 |
container_title |
Malaria Journal |
container_volume |
6 |
container_issue |
1 |
container_start_page |
108 |
_version_ |
1766341124294705152 |