Novel point mutations in sulfadoxine resistance genes of Plasmodium falciparum from India

Acta Tropica ◽  
2009 ◽  
Vol 110 (1) ◽  
pp. 75-79 ◽  
Author(s):  
Shilpi Garg ◽  
Vishal Saxena ◽  
Swarna Kanchan ◽  
Pooja Sharma ◽  
Siddharth Mahajan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Resistance Genes ◽  
Point Mutations

scholarly journals Reversal of Mefloquine and Quinine Resistance in Plasmodium falciparum with NP30

2003 ◽  
Vol 47 (8) ◽  
pp. 2393-2396 ◽  
Author(s):  
Michelle Ciach ◽  
Kathleen Zong ◽  
Kevin C. Kain ◽  
Ian Crandall
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistance ◽  
Genetic Analysis ◽  
Resistance Genes ◽  
Mammalian Cells ◽  
Point Mutations ◽  
In Vitro Assays ◽  
Drug Efflux ◽  
P Glycoprotein

ABSTRACT Quinoline resistance in malaria is frequently compared with P-glycoprotein-mediated multidrug resistance (mdr) in mammalian cells. We have previously reported that nonylphenolethoxylates, such as NP30, are potential Plasmodium falciparum P-glycoprotein substrates and drug efflux inhibitors. We used in vitro assays to compare the ability of verapamil and NP30 to sensitize two parasite isolates to four quinolines: chloroquine (CQ), mefloquine (MF), quinine (QN), and quinidine (QD). NP30 was able to sensitize (reversal, >80%) P. falciparum to MF, QN, QD, and, to a lesser extent, CQ. The presence of 2 μM verapamil had no effect on mefloquine resistance; however, the presence of verapamil modulated the activities of QN and QD in a manner parallel to that observed for CQ. Genetic analysis of putative quinoline resistance genes did not suggest an association between known point mutations in pfcrt and pfmdr1 and NP30 sensitization activity. We conclude that the sensitization action of NP30 is distinct both phenotypically and genotypically from that of verapamil.

scholarly journals Kenyan Plasmodium falciparum Field Isolates: Correlation between Pyrimethamine and Chlorcycloguanil Activity In Vitro and Point Mutations in the Dihydrofolate Reductase Domain

1998 ◽  
Vol 42 (1) ◽  
pp. 164-169 ◽  
Author(s):  
A. Nzila-Mounda ◽  
E. K. Mberu ◽  
C. H. Sibley ◽  
C. V. Plowe ◽  
P. A. Winstanley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Drug Response ◽  
Point Mutations ◽  
Distinct Group ◽  
Wild Type ◽  
Field Isolates ◽  
Vitro Data ◽  
In Vitro Data

ABSTRACT Sixty-nine Kenyan Plasmodium falciparum field isolates were tested in vitro against pyrimethamine (PM), chlorcycloguanil (CCG), sulfadoxine (SD), and dapsone (DDS), and their dihydrofolate reductase (DHFR) genotypes were determined. The in vitro data show that CCG is more potent than PM and that DDS is more potent than SD. DHFR genotype is correlated with PM and CCG drug response. Isolates can be classified into three distinct groups based on their 50% inhibitory concentrations (IC50s) for PM and CCG (P< 0.01) and their DHFR genotypes. The first group consists of wild-type isolates with mean PM and CCG IC50s of 3.71 ± 6.94 and 0.24 ± 0.21 nM, respectively. The second group includes parasites which all have mutations at codon 108 alone or also at codons 51 or 59 and represents one homogeneous group for which 25- and 6-fold increases in PM and CCG IC50s, respectively, are observed. Parasites with mutations at codons 108, 51, and 59 (triple mutants) form a third distinct group for which nine- and eightfold increases in IC50s, respectively, of PM and CCG compared to the second group are observed. Surprisingly, there is a significant decrease (P < 0.01) of SD and DDS susceptibility in these triple mutants. Our data show that more than 92% of Kenyan field isolates have undergone at least one point mutation associated with a decrease in PM activity. These findings are of great concern because they may indicate imminent PM-SD failure, and there is no affordable antimalarial drug to replace PM-SD (Fansidar).

scholarly journals Microevolution within ST11 group Clostridioides difficile isolates through mobile genetic elements based on complete genome sequencing

BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yuan Wu ◽  
Lin Yang ◽  
Wen-Ge Li ◽  
Wen Zhu Zhang ◽  
Zheng Jie Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Resistance Genes ◽  
Point Mutations ◽  
Evolutionary Process ◽  
Mobile Genetic Elements ◽  
Genetic Elements ◽  
Clostridioides Difficile ◽  
Hospitalized Elderly ◽  
Great Heterogeneity ◽  
High Level

Abstract Background Clade 5 Clostridioides difficile diverges significantly from the other clades and is therefore, attracting increasing attention due its great heterogeneity. In this study, we used third-generation sequencing techniques to sequence the complete whole genomes of three ST11 C. difficile isolates, RT078 and another two new ribotypes (RTs), obtained from three independent hospitalized elderly patients undergoing antibiotics treatment. Mobile genetic elements (MGEs), antibiotic-resistance, drug resistance genes, and virulent-related genes were analyzed and compared within these three isolates. Results Isolates 10,010 and 12,038 carried a distinct deletion in tcdA compared with isolate 21,062. Furthermore, all three isolates had identical deletions and point-mutations in tcdC, which was once thought to be a unique characteristic of RT078. Isolate 21,062 (RT078) had a unique plasmid, different numbers of transposons and genetic organization, and harboring special CRISPR spacers. All three isolates retained high-level sensitivity to 11 drugs and isolate 21,062 (RT078) carried distinct drug-resistance genes and loss of numerous flagellum-related genes. Conclusions We concluded that capillary electrophoresis based PCR-ribotyping is important for confirming RT078. Furthermore, RT078 isolates displayed specific MGEs, indicating an independent evolutionary process. In the further study, we could testify these findings with more RT078 isolates of divergent origins.

Detection of novel point mutations in the Plasmodium falciparum ATPase6 candidate gene for resistance to artemisinins

2008 ◽  
Vol 57 (2) ◽  
pp. 233-235 ◽  
Author(s):  
Michela Menegon ◽  
Anna Rosa Sannella ◽  
Giancarlo Majori ◽  
Carlo Severini
Keyword(s):  
Plasmodium Falciparum ◽  
Candidate Gene ◽  
Point Mutations

Prevalence of pfcrt point mutations and level of chloroquine resistance in Plasmodium falciparum isolates from Africa

2006 ◽  
Vol 6 (4) ◽  
pp. 262-268 ◽  
Author(s):  
Carlo Severini ◽  
Michela Menegon ◽  
Anna Rosa Sannella ◽  
Maria Grazia Paglia ◽  
Pasquale Narciso ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Point Mutations ◽  
Chloroquine Resistance

scholarly journals Increased Prevalence of Mutant Allele Pfdhps 437G and Pfdhfr Triple Mutation in Plasmodium falciparum Isolates from a Rural Area of Gabon, Three Years after the Change of Malaria Treatment Policy

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Jacques-Mari Ndong Ngomo ◽  
Denise Patricia Mawili-Mboumba ◽  
Noé Patrick M’Bondoukwe ◽  
Rosalie Nikiéma Ndong Ella ◽  
Marielle Karine Bouyou Akotet
Keyword(s):  
Plasmodium Falciparum ◽  
Dihydrofolate Reductase ◽  
Mutant Allele ◽  
Continuous Monitoring ◽  
Intermittent Preventive Treatment ◽  
Point Mutations ◽  
Preventive Treatment ◽  
Malaria Treatment ◽  
Pcr Rflp ◽  
Elevated Frequency

In Gabon, sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment during pregnancy (IPTp-SP) and for uncomplicated malaria treatment through ACTs drug. P. falciparum strains resistant to SP are frequent in areas where this drug is highly used and is associated with the occurrence of mutations on Plasmodium falciparum dihydrofolate reductase (Pfdhfr) and dihydropteroate synthetase (Pfdhps) genes. The aim of the study was to compare the proportion of mutations on Pfdhfr and Pfdhps genes in isolates collected at Oyem in northern Gabon, in 2005 at the time of IPTp-SP introduction and three years later. Point mutations were analyzed by nested PCR-RFLP method. Among 91 isolates, more than 90% carried Pfdhfr 108N and Pfdhfr 59R alleles. Frequencies of Pfdhfr 51I (98%) and Pfdhps 437G (67.7%) mutant alleles were higher in 2008. Mutations at codons 164, 540, and 581 were not detected. The proportion of the triple Pfdhfr mutation and quadruple mutation including A437G was high: 91.9% in 2008 and 64.8% in 2008, respectively. The present study highlights an elevated frequency of Pfdhfr and Pfdhps mutant alleles, although quintuple mutations were not found in north Gabon. These data suggest the need of a continuous monitoring of SP resistance in Gabon.

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