scholarly journals High resolution melting analysis and detection of Leishmania resistance: the role of multi drug resistance 1 gene

2021 ◽  
Vol 43 (1) ◽  
Author(s):  
Maryam Fekri Soofi Abadi ◽  
Alireza Moradabadi ◽  
Reza Vahidi ◽  
Saeedeh Shojaeepour ◽  
Sara Rostami ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Resolution ◽  
High Resolution Melting ◽  
Efflux Pump ◽  
Mdr1 Gene ◽  
Multi Drug Resistance ◽  
Sequencing Method ◽  
Melting Analysis ◽  
Resistance Protein

Abstract Background Pentavalent antimonial compounds are currently used to treat leishmaniasis and resistance to these drugs is a serious problem. Multidrug resistance protein is an efflux pump of the cell membrane that expels foreign compounds. This study designed to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene, in biopsy specimens of Leishmania tropica, with high resolution melting (HRM) method. In this experimental study, genomic DNA was extracted from 130 patients with skin leishmaniasis. Then, nucleotide changes were investigated throughout the gene using HRM and sequencing methods. The samples categorized in 5 groups by differences in the melting temperature (Tm). Result The nucleotide changes analysis showed that 61% of the samples of different groups that were unresponsive to drug had mutations in the MDR1 gene, which were also confirmed by the sequencing method. These mutations can be one of the factors responsible for non-responsiveness to the treatment. Conclusion According to the findings, it seems that mutation in MDR1 gene could be responsible for drug resistance to pentavalent antimonial compounds. Furthermore, HRM method can be used to diagnose drug resistance in leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the leishmania affected patients.

scholarly journals High Resolution Melting Analysis in Leishmania Resistance: The Role of Multi Drug Resistance 1 Gene

2020 ◽  
Author(s):  
Maryam Fekri Soofi Abadi ◽  
Alireza Moradabadi ◽  
Reza Vahidi ◽  
Iman Rad ◽  
Shahriar Dabiri
Keyword(s):  
Drug Resistance ◽  
High Resolution ◽  
Genomic Dna ◽  
High Resolution Melting ◽  
Mdr1 Gene ◽  
Multi Drug Resistance ◽  
Biopsy Specimens ◽  
Sequencing Method ◽  
Melting Analysis

Abstract Objective Pentavalent antimonial compounds are currently used to treat Leishmaniasis. Resistance to these drugs is a serious problem. The purpose of this study was to evaluate the mutations in the multi-drug resistance 1 (MDR1) gene in biopsy specimens of Leishmania Tropica with high resolution melting (HRM) method.Results In this experimental study, genomic DNA was extracted from 130 patients with skin Leishmaniasis. Then, nucleotide changes were investigated throughout the gene length using HRM and sequencing methods. The results of the nucleotide changes showed that 61% of the samples that were unresponsive to drug had mutations in the MDR1 gene in different groups, which were confirmed by the sequencing method. These mutations can be one of the factors responsible for non-response to the treatment of the disease. HRM method can be used to diagnose drug resistance in Leishmaniasis. It is also recommended that further studies be done regarding the importance of drug resistance in the affected patients.

scholarly journals Rapid Detection of Common HIV-1 Drug Resistance Mutations by Use of High-Resolution Melting Analysis and Unlabeled Probes

2016 ◽  
Vol 55 (1) ◽  
pp. 122-133 ◽  
Author(s):  
David Sacks ◽  
Johanna Ledwaba ◽  
Lynn Morris ◽  
Gillian M. Hunt
Keyword(s):  
Drug Resistance ◽  
High Resolution ◽  
High Resolution Melting ◽  
Antiretroviral Drugs ◽  
High Resolution Melting Analysis ◽  
Resistance Mutations ◽  
Drug Resistance Mutations ◽  
Melting Analysis ◽  
Analytical Sensitivities ◽  
Hiv 1

ABSTRACTHIV rapidly accumulates resistance mutations following exposure to subtherapeutic concentrations of antiretroviral drugs that reduces treatment efficacy. High-resolution melting analysis (HRMA) has been used to successfully identify single nucleotide polymorphisms (SNPs) and to genotype viral and bacterial species. Here, we tested the ability of HRMA incorporating short unlabeled probes to accurately assign drug susceptibilities at the 103, 181, and 184 codons of the HIV-1 reverse transcriptase gene. The analytical sensitivities of the HRMA assays were 5% of mixed species for K103N and Y181C and 20% for M184V. When applied to 153 HIV-1 patient specimens previously genotyped by Sanger population sequencing, HRMA correctly assigned drug sensitivity or resistance profiles to 80% of the samples at codon 103 (K103K/N) (Cohen's kappa coefficient [κ] > 0.6;P< 0.05), 90% at 181 (Y181Y/C) (κ > 0.74,P< 0.05), and 80% at 184 (M184M/V) (κ > 0.62;P< 0.05). The frequency of incorrect genotypes was very low (≤1 to 2%) for each assay, which in most cases was due to the higher sensitivity of the HRMA assay. Specimens for which drug resistance profiles could not be assigned (9 to 20%) often had polymorphisms in probe binding regions. Thus, HRMA is a rapid, inexpensive, and sensitive method for the determination of drug sensitivities caused by major HIV-1 drug resistance mutations and, after further development to minimize the melting effects of nontargeted polymorphisms, may be suitable for surveillance purposes.

scholarly journals Role of RND Efflux Pumps in Drug Resistance of Cystic Fibrosis Pathogens

Antibiotics ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 863
Author(s):  
Viola Camilla Scoffone ◽  
Gabriele Trespidi ◽  
Giulia Barbieri ◽  
Samuele Irudal ◽  
Elena Perrin ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Drug Resistance ◽  
Efflux Pump ◽  
Bacterial Species ◽  
Efflux Pumps ◽  
Burkholderia Cenocepacia ◽  
Multi Drug Resistance ◽  
Achromobacter Xylosoxidans ◽  
Rnd Efflux Pumps

Drug resistance represents a great concern among people with cystic fibrosis (CF), due to the recurrent and prolonged antibiotic therapy they should often undergo. Among Multi Drug Resistance (MDR) determinants, Resistance-Nodulation-cell Division (RND) efflux pumps have been reported as the main contributors, due to their ability to extrude a wide variety of molecules out of the bacterial cell. In this review, we summarize the principal RND efflux pump families described in CF pathogens, focusing on the main Gram-negative bacterial species (Pseudomonas aeruginosa, Burkholderia cenocepacia, Achromobacter xylosoxidans, Stenotrophomonas maltophilia) for which a predominant role of RND pumps has been associated to MDR phenotypes.

scholarly journals Detection of Two Drug-Resistance Mutants of the Cytomegalovirus by High-Resolution Melting Analysis

2015 ◽  
Vol 30 (4) ◽  
pp. 319-325 ◽  
Author(s):  
Xiao-Fan Chen ◽  
Tian-Run Li ◽  
Hong Yang ◽  
Yong Shao ◽  
Jie Zhang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
High Resolution ◽  
High Resolution Melting ◽  
High Resolution Melting Analysis ◽  
Melting Analysis ◽  
Resistance Mutants

scholarly journals Multi-drug Resistance Protein 4 (MRP4)-mediated Regulation of Fibroblast Cell Migration Reflects a Dichotomous Role of Intracellular Cyclic Nucleotides

2012 ◽  
Vol 288 (6) ◽  
pp. 3786-3794 ◽  
Author(s):  
Chandrima Sinha ◽  
Aixia Ren ◽  
Kavisha Arora ◽  
Chang-Suk Moon ◽  
Sunitha Yarlagadda ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Cell Migration ◽  
Cyclic Nucleotides ◽  
Fibroblast Cell ◽  
Multi Drug Resistance ◽  
Resistance Protein

Role of Yin Yang-1 (YY1) in the transcription regulation of the multi-drug resistance (MDR1) gene

2018 ◽  
Vol 59 (11) ◽  
pp. 2628-2638 ◽  
Author(s):  
Gabriela Antonio-Andrés ◽  
Jesus Rangel-Santiago ◽  
Belen Tirado-Rodríguez ◽  
Gustavo U. Martinez-Ruiz ◽  
Miguel Klunder-Klunder ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Transcription Regulation ◽  
Mdr1 Gene ◽  
Multi Drug Resistance ◽  
Yin Yang 1 ◽  
Yin Yang

scholarly journals Parental mosaicism in Marfan and Ehlers–Danlos syndromes and related disorders

2021 ◽  
Author(s):  
Bertrand Chesneau ◽  
Aurélie Plancke ◽  
Guillaume Rolland ◽  
Nicolas Chassaing ◽  
Christine Coubes ◽  
...  
Keyword(s):  
High Resolution ◽  
Marfan Syndrome ◽  
High Resolution Melting ◽  
De Novo ◽  
Direct Sequencing ◽  
Causal Variant ◽  
Connective Tissue Disorder ◽  
High Resolution Melting Analysis ◽  
Aortic Diseases ◽  
Melting Analysis

AbstractMarfan syndrome (MFS) is a heritable connective tissue disorder (HCTD) caused by pathogenic variants in FBN1 that frequently occur de novo. Although individuals with somatogonadal mosaicisms have been reported with respect to MFS and other HCTD, the overall frequency of parental mosaicism in this pathology is unknown. In an attempt to estimate this frequency, we reviewed all the 333 patients with a disease-causing variant in FBN1. We then used direct sequencing, combined with High Resolution Melting Analysis, to detect mosaicism in their parents, complemented by NGS when a mosaicism was objectivized. We found that (1) the number of apparently de novo events is much higher than the classically admitted number (around 50% of patients and not 25% as expected for FBN1) and (2) around 5% of the FBN1 disease-causing variants were not actually de novo as anticipated, but inherited in a context of somatogonadal mosaicisms revealed in parents from three families. High Resolution Melting Analysis and NGS were more efficient at detecting and evaluating the level of mosaicism compared to direct Sanger sequencing. We also investigated individuals with a causal variant in another gene identified through our “aortic diseases genes” NGS panel and report, for the first time, on an individual with a somatogonadal mosaicism in COL5A1. Our study shows that parental mosaicism is not that rare in Marfan syndrome and should be investigated with appropriate methods given its implications in patient’s management.

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