DHPS Gene

2020 ◽  
Author(s):  
Keyword(s):  
Dhps Gene

scholarly journals Low Prevalence of Pneumocystis pneumonia (PCP) but High Prevalence of Pneumocystis dihydropteroate synthase (dhps) Gene Mutations in HIV-Infected Persons in Uganda

PLoS ONE ◽  
2012 ◽  
Vol 7 (11) ◽  
pp. e49991 ◽  
Author(s):  
Steve M. Taylor ◽  
Steven R. Meshnick ◽  
William Worodria ◽  
Alfred Andama ◽  
Adithya Cattamanchi ◽  
...  
Keyword(s):  
Gene Mutations ◽  
Pneumocystis Pneumonia ◽  
Dihydropteroate Synthase ◽  
High Prevalence ◽  
Dhps Gene ◽  
Low Prevalence

scholarly journals Dihydropteroate synthase (DHPS) gene mutation study in HIV-Infected Indian patients with Pneumocystis jirovecii pneumonia

2010 ◽  
Vol 4 (11) ◽  
pp. 761-766 ◽  
Author(s):  
Anuj Kumar Tyagi ◽  
Bijay Ranjan Mirdha ◽  
Kalpana Luthra ◽  
Randeep Guleria ◽  
Anant Mohan ◽  
...  
Keyword(s):  
Silver Staining ◽  
Tertiary Care ◽  
Pneumocystis Carinii ◽  
Pneumocystis Jirovecii ◽  
Hiv Positive ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Sulfa Drug ◽  
Dihydropteroate Synthase ◽  
Methenamine Silver ◽  
Dhps Gene

Introduction: Pneumocystis jirovecii dihydropteroate synthase (DHPS) gene mutations' (55th and 57th codon) association with prior sulfa prophylaxis failure has been reported from both developed and developing countries. We conducted a prospective study to determine the prevalence of P. jirovecii DHPS mutations from 2006 to 2009 on P. jirovecii isolates obtained from HIV-infected patients with a clinical diagnosis of Pneumocystis carinii pneumonia (PCP) admitted to our tertiary care reference health center in New Delhi, India. Methodology: Detection of P. jirovecii cysts was performed by direct fluorescent antibody (DFA) staining and by Grocott's-Gomori methenamine silver staining (GMS). DNA detection was performed by polymerase chain reaction (PCR) using primers for the major surface glycoprotein (MSG) gene. P. jirovecii DHPS gene was amplified by nested PCR protocol and sequenced for detecting mutations at the 55th and 57th codons. Results: Out of 147 HIV-positive patients with suspected Pneumocystis pneumonia (PCP), 16 (10.8%) PCP positive cases were detected. Of 16 cases, nine (56.2%) were positive by DFA staining, four (25%) were positive by Grocott's-Gomori methenamine silver staining, and all 16 were positive by MSG PCR. DHPS mutations at the 55th and 57th codons were observed in 6.2% of HIV patients studied, which was relatively low compared to reports from developed nations. Conclusions:  Prevalence of Pneumocystis jirovecii DHPS mutations associated with cotrimoxazole treatment failure may be low in the Indian subpopulation of HIV-positive patients and warrants larger studies to elucidate the true picture of Pneumocystis jirovecii sulfa drug resistance in India.

PCR-RFLP Analysis of the DHPS gene for the Study of Resistance of Pneumocystis carinii to Sulpha Drugs in Patients with Co-infection PCP/HIV

2001 ◽  
Vol 48 ◽  
pp. 148s-149s ◽  
Author(s):  
MARINA C. COSTA ◽  
JANNICK HELWEG-LARSEN ◽  
FRANCISCO ANTUNES ◽  
BETTINA LUNGREN ◽  
JOSÉ DIOGO ◽  
...  
Keyword(s):  
Pneumocystis Carinii ◽  
Rflp Analysis ◽  
Sulpha Drugs ◽  
Pcr Rflp ◽  
Dhps Gene

Low-Dose Treatment with Sulfadoxine-Pyrimethamine Combinations Selects for Drug-Resistant Plasmodium falciparum Strains

1999 ◽  
Vol 43 (9) ◽  
pp. 2205-2208 ◽  
Author(s):  
Jürgen F. J. Kun ◽  
Leopold G. Lehman ◽  
Bertrand Lell ◽  
Ruprecht Schmidt-Ott ◽  
Peter G. Kremsner
Keyword(s):  
Low Dose ◽  
Point Mutations ◽  
Drug Resistant ◽  
Dhfr Gene ◽  
Dihydropteroate Synthase ◽  
Before And After ◽  
Genes Encoding ◽  
Resistant Strains ◽  
Dhps Gene ◽  
Drug Resistant Strains

ABSTRACT A total of 252 children were enrolled in a drug trial to assess the effect of minimal doses of sulfadoxine (Sdx) and pyrimethamine (Pyr). Parasite samples isolated from these patients were analyzed before and after treatment to investigate the level of drug-resistant strains. The parasite genes encoding dihydrofolate reductase (DHFR) and dihydropteroate synthase (DHPS) were assayed for point mutations that are associated with resistance against drugs. Before treatment, Pyrr genotypes of the DHFR gene were found in 42% of all samples, 8% of the patients harbored a mixed parasite population and 50% had a sensitive DHFR genotype. In terms of the DHPS gene, we found mutations in 45% of the parasites. Twenty-four percent had a Ser436 mutation, and 26% had a Gly437mutation. Recrudescent parasites were highly enriched for both Pyrr and Sdxr strains after treatment (P < 0.001 and P = 0.029, respectively).

scholarly journals In Vitro Susceptibility of Various Genotypic Strains of Toxoplasma gondii to Pyrimethamine, Sulfadiazine, and Atovaquone

2008 ◽  
Vol 52 (4) ◽  
pp. 1269-1277 ◽  
Author(s):  
Pascale Meneceur ◽  
Marie-Anne Bouldouyre ◽  
Dominique Aubert ◽  
Isabelle Villena ◽  
Jean Menotti ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Cell Cultures ◽  
Growth Kinetics ◽  
Target Genes ◽  
Drug Susceptibility ◽  
Enzyme Linked Immunosorbent Assay ◽  
Genotype I ◽  
In Vitro Susceptibility ◽  
Dhps Gene

ABSTRACT Sulfadiazine, pyrimethamine, and atovaquone are widely used for the treatment of severe toxoplasmosis. Their in vitro activities have been almost exclusively demonstrated on laboratory strains belonging to genotype I. We determined the in vitro activities of these drugs against 17 strains of Toxoplasma gondii belonging to various genotypes and examined the correlations among 50% inhibitory concentrations (IC50s), growth kinetics, strain genotypes, and mutations on drug target genes. Growth kinetics were determined in THP-1 cell cultures using real-time PCR. IC50s were determined in MRC-5 cell cultures using a T. gondii-specific enzyme-linked immunosorbent assay performed on cultures. Mutations in dihydrofolate reductase (DHFR), dihydropteroate synthase (DHPS), and cytochrome b genes were determined by sequencing. Pyrimethamine IC50s ranged between 0.07 and 0.39 mg/liter, with no correlation with the strain genotype but a significant correlation with growth kinetics. Several mutations found on the DHFR gene were not linked to lower susceptibility. Atovaquone IC50s were in a narrow range of concentrations (mean, 0.06 ± 0.02 mg/liter); no mutation was found on the cytochrome b gene. IC50s for sulfadiazine ranged between 3 and 18.9 mg/liter for 13 strains and were >50 mg/liter for three strains. High IC50s were not correlated to strain genotypes or growth kinetics. A new mutation of the DHPS gene was demonstrated in one of these strains. In conclusion, we found variability in the susceptibilities of T. gondii strains to pyrimethamine and atovaquone, with no evidence of drug resistance. A higher variability was found for sulfadiazine, with a possible resistance of three strains. No relationship was found between drug susceptibility and strain genotype.

scholarly journals Rapid Detection of Mutations in the Human-DerivedPneumocystis carinii Dihydropteroate Synthase Gene Associated with Sulfa Resistance

2001 ◽  
Vol 45 (3) ◽  
pp. 776-780 ◽  
Author(s):  
Liang Ma ◽  
Joseph A. Kovacs
Keyword(s):  
Rapid Detection ◽  
Direct Sequencing ◽  
Pneumocystis Carinii ◽  
Point Mutations ◽  
Single Strand Conformation Polymorphism ◽  
Rapid Identification ◽  
Clinical Isolates ◽  
Minority Population ◽  
Dihydropteroate Synthase ◽  
Dhps Gene

ABSTRACT Recent studies have shown that point mutations in the dihydropteroate synthase (DHPS) gene of human-derivedPneumocystis carinii are related to exposure to sulfa drugs and possibly represent the emergence of sulfa resistance. We developed a simple single-strand conformation polymorphism (SSCP) method to permit rapid detection of these mutations. With plasmid constructs, SSCP was able to detect as little as 10% of a minority population. The SSCP assay was compared to direct sequencing for typing the DHPS gene by examining 37 clinical isolates with known DHPS sequences and 41 clinical isolates with unknown DHPS sequences. The typing results were consistent between these two methods for all isolates except 11 in which mutations were detected by SSCP but not by direct sequencing. Sequencing of individual clones after subcloning confirmed the presence of mutations in a minority population as determined by SSCP. SSCP is a very simple and sensitive method for rapid identification of P. camii DHPS mutations.

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