Susceptibility in vitro of clinically metronidazole-resistant Trichomonas vaginalis to nitazoxanide, toyocamycin, and 2-fluoro-2′-deoxyadenosine

Wright, Janelle M.; Dunn, Linda A.; Kazimierczuk, Zygmunt; Burgess, Anita; Krauer, Kenia G.; Upcroft, Peter; Upcroft, Jacqueline

doi:10.1007/s00436-010-1938-3

Cited by 25 publications

(22 citation statements)

References 54 publications

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“…Conversely, primary resistance of Giardia to nitazoxanide was reported to lead to significant but less complete resistance to Mz (26). Similar 5-NI drug crossresistance was observed in T. vaginalis (6,44), while Mz r H. pylori remained sensitive to other 5-NI compounds and to nitazoxanide (32,38). These data suggest that the mechanisms of 5-NI drug resistance overlap in different microbes, but they are not the same for different structural classes of nitro drugs.…”

Section: Discussionmentioning

confidence: 84%

Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia

Tejman-Yarden

Millman

Lauwaet

et al. 2011

Antimicrob Agents Chemother

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Infections with the diarrheagenic protozoan pathogen Giardia lamblia are most commonly treated with metronidazole (Mz). Treatment failures with Mz occur in 10 to 20% of cases and Mz resistance develops in the laboratory, yet clinically, Mz-resistant (Mz r ) G. lamblia has rarely been isolated from patients. To understand why clinical Mz r isolates are rare, we questioned whether Mz resistance entails fitness costs to the parasite. Our studies employed several newly generated and established isogenic Mz r cell lines with stable, high-level resistance to Mz and significant cross-resistance to tinidazole, nitazoxanide, and furazolidone. Oral infection of suckling mice revealed that three of five Mz r cell lines could not establish infection, while two Mz r cell lines infected pups, albeit with reduced efficiencies. Failure to colonize resulted from a diminished capacity of the parasite to attach to the intestinal mucosa in vivo and to epithelial cells and plastic surfaces in vitro. The attachment defect was related to impaired glucose metabolism, since the noninfectious Mz r lines consumed less glucose, and glucose promoted ATP-independent parasite attachment in the parental lines. Thus, resistance of Giardia to Mz is accompanied by a glucose metabolism-related attachment defect that can interfere with colonization of the host. Because glucose-metabolizing pathways are important for activation of the prodrug Mz, it follows that a fitness trade-off exists between diminished Mz activation and reduced infectivity, which may explain the observed paucity of clinical Mz r isolates of Giardia. However, the data also caution that some forms of Mz resistance do not markedly interfere with in vivo infectivity.

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Section: Discussionmentioning

confidence: 84%

Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia

Tejman-Yarden

Millman

Lauwaet

et al. 2011

Antimicrob Agents Chemother

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“…2. This assay was performed according to Wright et al (2010) and Delmas et al (2002) with modifications. Amomum tsao-ko essential oil and geraniol were diluted by geometric dilutions in 96-well plates, ranging from 22.48 mg/ ml to 46.05 mg/ml of A. tsao-ko essential oil, and from 21.43 mg/ml to 43.90 mg/ml of geraniol.…”

Section: Determination Of Minimum Lethal Concentration (Mlc) and 50% mentioning

confidence: 99%

“…Moreover, an increasing number of metronidazole-resistant T. vaginalis isolates have been reported since metronidazole was introduced for the treatment of trichomoniasis in 1959 (Blaha et al, 2006;Butler et al, 2010;Durel et al, 1967;Narcisi & Secor, 1996;Schmid et al, 2001; Upcroft et al, 2006). In addition, the metronidazole-resistant isolates were cross-resistant to other members of the 5-nitrothiazole compounds including ornidazole, tinidazole, nitazoxanide, and furazolidone (Wright et al, 2010). Therefore, to improve the current chemotherapy against T. vaginalis infection, the natural products with high effectiveness and low toxicity may be an alternative therapeutic source.…”

Section: Introductionmentioning

confidence: 99%

Anti-Trichomonas vaginalisproperties of the oil ofAmomum tsao-koand its major component, geraniol

Dai

Peng

et al. 2015

Pharmaceutical Biology

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Context: Trichomonosis, caused by the flagellate protozoan Trichomonas vaginalis, is the most common non-viral sexually transmitted disease (STD) and 5-nitroimidazole drugs are used for the treatment. However, a growing number of T. vaginalis isolates are resistant to these drugs, which make it becomes an urgent issue. Objective: The current study was designed to evaluate the anti-T. vaginalis activity of the essential oil from A. tsao-ko used in traditional Chinese medicine and as a spice and its main component, geraniol. Materials and methods:The anti-T. vaginalis activities of A. tsao-ko essential oil and geraniol were evaluated by the minimum lethal concentration (MLC) and 50% inhibitory concentration (IC 50 ) in vitro. The morphological changes of T. vaginalis were observed by transmission electron microscopy (TEM). Additionally, sub-MLC concentration treatment with sub-MLC A. tsao-ko essential oil and geraniol was also performed. Results: This study shows that MLC/IC 50 of A. tsao-ko essential oil was 44.97 mg/ml/22.49 mg/ml for T. vaginalis isolate Tv1, and 89.93 mg/ml/44.97 mg/ml for T. vaginalis isolate Tv2. Those of geraniol were 342.96 mg/ml/171.48 mg/ml, respectively. After A. tsao-ko essential oil or geraniol treatment, obvious similar morphological changes of T. vaginalis were observed by TEM: the nuclear membrane was damaged, nuclei were dissolved, and the chromatin was accumulated; in the cytoplasm, numerous vacuoles appeared, rough endoplasmic reticulum dilated, the number of ribosomes were reduced, organelles disintegrated, the cell membrane was partially damaged, with cytoplasmic leakage, and cell disintegration was observed. The action time did not increase the effect of A. tsao-ko essential oil or geraniol against T. vaginalis, as no significant difference was observed after sub-MLC concentration treatment for 1, 3, and 5 h with A. tsao-ko essential oil and geraniol. Discussion and conclusion: The study describes the first report on the activity and morphological changes of A. tsao-ko essential oil and geraniol against T. vaginalis. The results obtained herein presented new opportunities for antitrichomonal drugs.

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“…Wright et al (17) has studied some metronidazole-resistant isolates, having a microaerobic minimal inhibitory concentration (MIC) of 50 -100 μ m , instead of susceptible isolates characterized by 3.2 μ m , of metronidazole. Nitazoxamide, toyocamycin, and 2-fluoro-2 ′ -deoxyadenosine were used by Wright et al (17) to test susceptible and resistant T. vaginalis isolates. Under 6% O 2 assay conditions, the susceptible isolates were also susceptible to the three new drugs tested, and had MICs of 1.6 -6 μ m .…”

Section: ′ -Deoxyadenosine Analogs As Drugsmentioning

confidence: 99%

“…Vivet-Boudou et al (16) studied how C8-modified 2 ′ -deoxyadenosine analogs induce delayed polymerization arrest in HIV-1 reverse transcriptase. Wright et al (17) studied some metronidazole-resistant isolates of Trichomonas vaginalis , finding that some such strains were susceptible to toyocamycin and 2-fluoro-2 ′ -deoxyadenosine, two 2 ′ -deoxyadenosine analogs, whereas some are moderately susceptible. GS-9148 is a dAMP analog having antiviral activity against drug-resistant HIV.…”

Section: Introductionmentioning

confidence: 99%

Deoxyadenosine family: improved synthesis, DNA damage and repair, analogs as drugs

Biswas

Kar

Chattopadhyaya

2013

BioMolecular Concepts

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Improved synthesis of 2 ′ -deoxyadenosine using Escherichia coli overexpressing some enzymes and gram-scale chemical synthesis of 2 ′ -deoxynucleoside 5 ′ -triphosphates reported recently are described in this review. Other topics include DNA damage induced by chromium(VI), Fenton chemistry, photoinduction with lumazine, or by ultrasound in neutral solution; 8,5 ′ -cyclo-2 ′ -deoxyadenosine isomers as potential biomarkers; and a recapitulation of purine 5 ′ ,8-cyclonucleoside studies. The mutagenicities of some products generated by oxidizing 2 ′ -deoxyadenosine 5 ′ -triphosphate, nucleotide pool sanitization, and translesion synthesis are also reviewed. Characterizing cross-linking between nucleosides in opposite strands of DNA and endonuclease V-mediated deoxyinosine excision repair are discussed. The use of purine nucleoside analogs in the treatment of rarer chronic lymphoid leukemias is reviewed. Some analogs at the C8 position induced delayed polymerization arrest during HIV-1 reverse transcription. The susceptibility of clinically metronidazole-resistant Trichomonas vaginalis to two analogs, toyocamycin and 2-fluoro-2 ′ -deoxyadenosine, were tested in vitro . GS-9148, a dAMP analog, was translocated to the priming site in a complex with reverse transcriptase and double-stranded DNA to gain insight into the mechanism of reverse transcriptase inhibition.

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Susceptibility in vitro of clinically metronidazole-resistant Trichomonas vaginalis to nitazoxanide, toyocamycin, and 2-fluoro-2′-deoxyadenosine

Cited by 25 publications

References 54 publications

Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia

Impaired Parasite Attachment as Fitness Cost of Metronidazole Resistance in Giardia lamblia

Anti-Trichomonas vaginalisproperties of the oil ofAmomum tsao-koand its major component, geraniol

Deoxyadenosine family: improved synthesis, DNA damage and repair, analogs as drugs

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