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Antimicrobial Agents and Chemotherapy, May 2003, p. 1658-1664, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1658-1664.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Molecular Evaluation of Antibiotic Susceptibility: Tropheryma whipplei Paradigm

F. Masselot, A. Boulos, M. Maurin, J. M. Rolain, and D. Raoult*

Unité des Rickettsies, CNRS UMR 6020, Faculté de Médecine, Université de la Méditerranée, 13385 Marseille Cedex 05, France

Received 4 October 2002/ Returned for modification 19 November 2002/ Accepted 10 February 2003

Tropheryma whipplei, the agent of Whipple's disease, grows fastidiously only in cell cultures without plaque production, and only three strains have been passaged. The formation of bacterial clumps in the supernatant precludes enumeration of viable bacteria and MIC determination. We evaluated the bacteriostatic effects of fluoroquinolones against two T. whipplei isolates by measuring the inhibition of the DNA copy number increase by real-time quantitative PCR. The analysis of the T. whipplei genome database allowed the identification not only of the gyrA gene but also the parC gene encoding the alpha subunit of the natural fluoroquinolone targets DNA gyrase (GyrA) and topoisomerase IV (ParC), respectively. The parC gene was detected in actinobacteria for the first time. High ciprofloxacin MICs (4 and 8 µg/ml) were correlated with the presence in T. whipplei GyrA and ParC sequences with an alanine residue at positions 83 and 80 (Escherichia coli numbering), respectively. Alanines at these positions have previously been associated with increased fluoroquinolone resistance in E. coli and mycobacteria. However, the MIC of levofloxacin was low (0.25 µg/ml). The same T. whipplei GyrA and ParC sequences were found in two other cultured strains and in nine uncultured tissue samples from Whipple's disease patients, allowing one to speculate that T. whipplei is naturally relatively resistant to fluoroquinolones.

* Corresponding author. Mailing address: Unité des Rickettsies, CNRS UMR 6020, IFR48, Faculté de Médecine, Université de la Méditerranée, 27 Boulevard Jean Moulin, 13385 Marseille Cedex 05, France. Phone: (33) 4 91 38 55 17. Fax: (33) 4 91 83 03 90. E-mail: Didier.Raoult{at}medecine.univ-mrs.fr.

Antimicrobial Agents and Chemotherapy, May 2003, p. 1658-1664, Vol. 47, No. 5
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.5.1658-1664.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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