Introducing nitazoxanide as a promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in clinical isolates

Galeh, Tahereh Mikaeili; Kazemi, Abdolhassan; Mahami-Oskouei, Mahmoud; Baradaran, Behzad; Spotin, Adel; Sarafraz, Seddigheh; Karamat, Majid

doi:10.1016/j.apjtm.2016.07.013

Cited by 16 publications

(14 citation statements)

References 28 publications

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“…Begaydarova et al 2015 investigated clinical isolates and linked PFOR gene expression to MTZ resistance, but PFOR was not found to be a good resistance marker 40. Another study by Galeh et al 201641 linked non-synonymous single nucleotide variants (nsSNVs) in PFOR and NR genes to MTZ resistance and possibly through reduced translation and thereby reduced MTZ activation. Genetic variation in Giardia genome is not well known, except for a few genotyping genes, ie, triose phosphate isomerase ( tpi), glutamate dehydrogenase ( gdh ) and beta-giardin ( bg ) 42.…”

Section: Introductionmentioning

confidence: 99%

Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical Giardia lamblia assemblage A and B isolates

Saghaug

Klotz

Kallio

et al. 2019

IDR

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Purpose: Treatment-refractory Giardia cases have increased rapidly within the last decade. No markers of resistance nor a standardized susceptibility test have been established yet, but several enzymes and their pathways have been associated with metronidazole (MTZ) resistant Giardia . Very limited data are available regarding genetic variation in these pathways. We aimed to investigate genetic variation in metabolic pathway genes proposed to be involved in MTZ resistance in recently acquired, cultured clinical isolates. Methods: Whole genome sequencing of 12 assemblage A2 and 8 assemblage B isolates was done, to decipher genomic variation in Giardia . Twenty-nine genes were identified in a literature search and investigated for their single nucleotide variants (SNVs) in the coding/non-coding regions of the genes, either as amino acid changing (non-synonymous SNVs) or non-changing SNVs (synonymous). Results: In Giardia assemblage B, several genes involved in MTZ activation or oxidative stress management were found to have higher numbers of non-synonymous SNVs (thioredoxin peroxidase, nitroreductase 1, ferredoxin 2, NADH oxidase, nitroreductase 2, alcohol dehydrogenase, ferredoxin 4 and ferredoxin 1) than the average variation. For Giardia assemblage A2, the highest genetic variability was found in the ferredoxin 2, ferredoxin 6 and in nicotinamide adenine dinucleotide phosphate (NADPH) oxidoreductase putative genes. SNVs found in the ferredoxins and nitroreductases were analyzed further by alignment and homology modeling. SNVs close to the iron-sulfur cluster binding sites in nitroreductase-1 and 2 and ferredoxin 2 and 4 could potentially affect protein function. Flavohemoprotein seems to be a variable-copy gene, due to higher, but variable coverage compared to other genes investigated. Conclusion: In clinical Giardia isolates, genetic variability is common in important genes in the MTZ metabolizing pathway and in the management of oxidative and nitrosative stress and includes high numbers of non-synonymous SNVs. Some of the identified amino acid changes could potentially affect the respective proteins important in the MTZ metabolism.

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Section: Introductionmentioning

confidence: 99%

Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical Giardia lamblia assemblage A and B isolates

Saghaug

Klotz

Kallio

et al. 2019

IDR

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“…In vitro studies have induced resistance. Crucially, studies have shown conflicting results, as some metronidazole resistant lines display nitazoxanide susceptibility and others cross-resistance [11,16,31,48]. Primary resistance is thought to be due to altered expression of stress response proteins [48].…”

Section: Nitazoxanidementioning

confidence: 99%

“…Furazolidone undergoes reduction, utilizing NADH oxidase, to produce superoxide radicals. These damage DNA and functional organelles, reducing the trophozoites' ability to differentiate into cysts [7,19,31,33,60]. When used as initial therapy, it has a similar efficacy to metronidazole, with a cure rate of 80e96% [7,34].…”

Section: Furazolidonementioning

confidence: 99%

Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions

Carter

Nabarro

Hedley

et al. 2018

Clinical Microbiology and Infection

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“…Metronidazole (MTZ, 1‐(2‐hydroxyethyl)‐2‐methyl‐5‐nitroimidazole) is a well‐known nitroimidazole derivative, that performs as an effective medicine against anaerobic bacteria, trichomonas, amoeba and giardia and so on. However, overload of MTZ will potentially exert carcinogenic, teratogenic, mutagenic and genetic toxicities to humans.…”

Section: Introductionmentioning

confidence: 99%

Detection of metronidazole in honey and metronidazole tablets using carbon dots‐based sensor via the inner filter effect

et al. 2018

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In this work, carbon dots (CDs) with a high quantum yield (22.3%) were easily prepared by hydrothermal pyrolysis of acid fuchsin 6B and hydrogen peroxide at 180°C for 10 h. The resultant CDs possess a narrow size distribution in the range of 2.6 to 3.2 nm and emit blue fluorescence. Interestingly, the absorption band of metronidazole (MTZ) centered at 318 nm can complementary overlap with the excitation band of the as-prepared CDs centered at 320 nm, resulting in an inner filter effect (IFE) in high efficiency. In fact, the fluorescence quenching of the CDs depends on the concentration of MTZ. Therefore, a simple method for the detection of MTZ can be established using the CDs-based sensor via the IFE. The linear range of the proposed method was 0-10 μg mL with the limit of detection as low as 0.257 μg mL . This CDs-based sensor had been applied for the detection of MTZ in honey and MTZ tablets with the recoveries in the range of 98.0% to 105.1% and 95.7% to 106.5%, respectively. Therefore, the as-prepared CDs have a potential to be developed as a MTZ sensor with high selectivity, sensitivity and accuracy.

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Introducing nitazoxanide as a promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in clinical isolates

Cited by 16 publications

References 28 publications

<p>Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical<em> Giardia lamblia</em> assemblage A and B isolates</p>

<p>Genetic variation in metronidazole metabolism and oxidative stress pathways in clinical<em> Giardia lamblia</em> assemblage A and B isolates</p>

Nitroimidazole-refractory giardiasis: a growing problem requiring rational solutions

Detection of metronidazole in honey and metronidazole tablets using carbon dots‐based sensor via the inner filter effect

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