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In vitro activity of pentamidine against Tropheryma whipplei
Jean-Marc Rolain1, Florence Fenollar, Didier Raoult
1Unité de Recherche sur Maladies Infectieuses et Tropicales Emergents, CNRS-IRD, UMR 6236, Faculté de Médecine et de Pharmacie, Université de Méditerranée Aix-Marseille II, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France. jean-marc.rolain@univmed.fr
Abstract:
Pentamidine is a group I intron splice inhibitor used as a chemotherapeutic agent to treat parasitic infections. It was recently found to be efficient intracellularly against Coxiella burnetii, the bacterial agent of Q fever. This in vitro activity was linked to the presence of self-splicing group I introns that disrupt the 23S rRNA of C. burnetii. However, there are several indications that pentamidine may have a wider range of antibacterial activity. The aim of this study was to determine the in vitro activity of pentamidine against Tropheryma whipplei, the agent of Whipple's disease, a chronic disease for which antibiotic treatment remains challenging. In vitro susceptibility testing of pentamidine and doxycycline was assessed both in axenic medium and in cell culture against three clinical isolates of T. whipplei using a quantitative real-time polymerase chain reaction (PCR) assay as previously described. Both doxycycline and pentamidine were found to be active against T. whipplei strains both in axenic medium and in cell culture, with minimum inhibitory concentration ranges of 0.5-1mg/L and 0.125-0.25mg/L for doxycycline and pentamidine, respectively. Pentamidine was effective in vitro against T. whipplei both intracellularly and in axenic medium. This is the first evidence of the direct efficacy of pentamidine against T. whipplei grown in axenic medium and in cells. Since pentamidine has been widely used in humans, we believe that it could be an alternative drug for the treatment of this chronic disease that should be further studied in clinical trials.
Insights
Pentamidine shows promising in vitro antibacterial activity against Tropheryma whipplei, the cause of Whipple's disease. This study suggests pentamidine could be a potential alternative treatment for this challenging chronic infection.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Pentamidine is a known splice inhibitor effective against parasitic infections.
- Recent studies indicate pentamidine's intracellular efficacy against Coxiella burnetii.
- The mechanism involves disruption of bacterial 23S rRNA by group I introns.
Purpose of the Study:
- To evaluate the in vitro antibacterial activity of pentamidine against Tropheryma whipplei.
- To assess pentamidine's efficacy in both axenic medium and cell cultures.
- To compare pentamidine's activity with doxycycline, a standard treatment.
Main Methods:
- In vitro susceptibility testing of pentamidine and doxycycline against three T. whipplei clinical isolates.
- Quantitative real-time PCR assay used for bacterial quantification.
- Testing conducted in both axenic medium and infected cell cultures.
Main Results:
- Pentamidine demonstrated significant in vitro activity against T. whipplei.
- Minimum inhibitory concentrations (MICs) for pentamidine ranged from 0.125-0.25 mg/L.
- Pentamidine was effective both intracellularly and in axenic conditions, outperforming doxycycline in some assays.
Conclusions:
- Pentamidine exhibits direct in vitro efficacy against Tropheryma whipplei.
- This is the first report of pentamidine's activity against T. whipplei in axenic and cell culture settings.
- Pentamidine warrants further investigation in clinical trials as a potential therapeutic agent for Whipple's disease.
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