Characterization of a Giardia lamblia WB C6 clone resistant to the isoflavone formononetin

Sterk, Maaike; Müller, Joachim; Hemphill, Andrew; Müller, Norbert

doi:10.1099/mic.0.2007/010041-0

Cited by 16 publications

(11 citation statements)

References 34 publications

(35 reference statements)

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“…Although treatment failures and drug resistance in Giardia can be problematic, a comparably large number of effective drugs are available, and combination therapy is almost always successful. Moreover, promising novel treatment options have been presented recently, such as formononetin [ 89 , 90 ], auranofin [ 5 •] and fumagillin [ 6 •], and natural products with antigiardial activity have remained an as yet untapped source [ 91 ].…”

Section: Discussionmentioning

confidence: 99%

Drug Resistance in the Microaerophilic Parasite Giardia lamblia

Leitsch

2015

Curr Trop Med Rep

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The microaerophilic parasite Giardia lamblia is a causative agent of dysentery affecting hundreds of millions of people around the globe every year. The symptoms of the disease, commonly referred to as giardiasis, are diarrhea, nausea, and malabsorption. Treatment of giardiasis is exclusively based on chemotherapy with antigiardial drugs, including metronidazole, albendazole, and nitazoxanide. In this review, all drugs currently used in the treatment of Giardia infections are discussed with a special emphasis on treatment failure and drug resistance.

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Section: Discussionmentioning

confidence: 99%

Drug Resistance in the Microaerophilic Parasite Giardia lamblia

Leitsch

2015

Curr Trop Med Rep

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“…There is precedence from individual cases in which combinations of currently used antigiardial drugs have been successfully applied for the treatment of patients refractory to single medication [39]. It should be noted that G. duodenalis is able to rapidly develop resistance against drugs in vitro [11], [40]. Although a similar effect against orlistat cannot yet be excluded, the use of drugs in combination may be therapeutically advantageous in that the development of drug resistance is hampered.…”

Section: Discussionmentioning

confidence: 99%

High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

et al. 2013

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Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment failure rates of up to 20 percent reflect the compelling need for alternative treatment options. Here, we investigated whether orlistat, a drug approved to treat obesity, represents a potential therapeutic agent against giardiasis. We compared the growth inhibitory effects of orlistat and MTZ on a long-term in vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14-03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The giardiacidal concentration of the drugs and their combined in vitro efficacy was determined by median-effect analysis. Morphological changes after treatment were analysed by light and electron microscopy. Orlistat inhibited the in vitro growth of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7 (IC5024h = 2.8 µM) being more sensitive than WB-C6 (IC5024h = 6.2 µM). The effect was significantly more potent compared to MTZ (IC5024h = 4.3 µM and 11.0 µM, respectively) and led to specific undulated morphological alterations on the parasite surface. The giardiacidal concentration of orlistat was >14 µM for 14-03/F7 and >43 µM for WB-C6, respectively. Importantly, the combination of both drugs revealed no interaction on their inhibitory effects. We demonstrate that orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills parasites at concentrations achievable in the gut by approved treatment regimens for obesity. We therefore propose to investigate orlistat in controlled clinical studies as a new drug in giardiasis.

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“…This is because it was recently suggested that formononetin impaired fl agellar motility (Lauwaet et al, 2010) which may participate in the suction force generated underneath the adhesive disk (Holberton, 1974) while Sterk et al (2007) showed that a giardial purine-metabolizing enzyme (nucleoside hydrolase) was bound and inactivated by isofl avones, and the expression levels of this enzyme are decreased in formononetin-resistant Giardia. Indeed trophozoites treated with the O-methylated isofl avone formononetin lost rapidly the adhesion ability to biologic and inert substrates by a yet undefi ned mechanism.…”

Section: Molecular Factors Involved In Giardia Adhesion To Host Cellsmentioning

confidence: 99%

“…duodenalis trophozoites can develop drug resistance to standard anti-parasitic treatments Muller et al, 2007;Sterk et al, 2007), and refractory giardiasis due to parasite drug resistance has been reported in both healthy and immunocompromised individuals (Abboud et al, 2001;Aronson et al, 2001;Hanevik et al, 2007;Morch et al, 2008). duodenalis trophozoites can develop drug resistance to standard anti-parasitic treatments Muller et al, 2007;Sterk et al, 2007), and refractory giardiasis due to parasite drug resistance has been reported in both healthy and immunocompromised individuals (Abboud et al, 2001;Aronson et al, 2001;Hanevik et al, 2007;Morch et al, 2008).…”

Section: Clinical Manifestations Of Giardiasismentioning

confidence: 99%

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Giardia

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Characterization of a Giardia lamblia WB C6 clone resistant to the isoflavone formononetin

Cited by 16 publications

References 34 publications

Drug Resistance in the Microaerophilic Parasite Giardia lamblia

Drug Resistance in the Microaerophilic Parasite Giardia lamblia

High Sensitivity of Giardia duodenalis to Tetrahydrolipstatin (Orlistat) In Vitro

Giardia

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