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Antimicrobial Agents and Chemotherapy, July 2001, p. 2098-2105, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2098-2105.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

DNA Gyrase-Mediated Natural Resistance to Fluoroquinolones in Ehrlichia spp.

M. Maurin,1 C. Abergel,2 and D. Raoult1,*

Unité des Rickettsies, CNRS UPRES A 6020, Université de la Méditerranée, Faculté de Médecine, 13385 Marseille Cedex 05,1 and Information Genetique et Structurale, UMR1889 CNRS-AVENTIS, 13402 Marseille Cedex 20,2 France

Received 29 January 2001/Returned for modification 19 March 2001/Accepted 20 April 2001

Fluoroquinolone susceptibility heterogeneity between various Ehrlichia species has been previously demonstrated. In gram-negative bacteria, resistance to fluoroquinolones most often corresponds to specific amino acid variations in a portion of the protein sequence of the A subunit of DNA gyrase (GyrA), referred to as the quinolone resistance-determining region (QRDR). We suspected a similar mechanism to be responsible for natural resistance in some Ehrlichia species. To verify this hypothesis, we sequenced the entire gyrA gene of the quinolone-susceptible species Ehrlichia sennetsu and designed specific primers to amplify and sequence the QRDR of four other Ehrlichia species as well as the closely related species Cowdria ruminantium. We identified in the fluoroquinolone-resistant species Ehrlichia chaffeensis and Ehrlichia canis a specific GyrA QRDR amino acid sequence, also present in C. ruminantium (whose susceptibility to fluoroquinolones remains unknown). These three species belong to a single phylogenetic cluster referred to as the E. canis genogroup. A different GyrA QRDR pattern, shared by the Ehrlichia species representatives of the E. sennetsu and Ehrlichia phagocytophila genogroups, was identified. Three of the four species tested are known to be susceptible to fluoroquinolones. A serine residue in position 83 (Escherichia coli numbering) in the susceptible species is replaced by an alanine residue in fluoroquinolone-resistant species. These results are consistent with the current knowledge on fluoroquinolone resistance in other gram-negative bacteria. They are indicative of a natural gyrase-mediated resistance to fluoroquinolones in the E. canis genogroup.

* Corresponding author. Mailing address: Unité des Rickettsies, CNRS UPRES A 6020, 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, July 2001, p. 2098-2105, Vol. 45, No. 7
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.7.2098-2105.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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