JAC Advance Access originally published online on April 21, 2007
Journal of Antimicrobial Chemotherapy 2007 59(6):1065-1070; doi:10.1093/jac/dkm105
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Molecular mechanisms of resistance to antibiotics in Bartonella bacilliformis
Unité des Rickettsies, CNRS UMR 6020, IFR 48, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France
Received 19 January 2007; returned 28 January 2007; revised 12 March 2007; accepted 16 March 2007
* Corresponding author. Tel: +33-491-38-55-17; Fax: +33-491-83-03-90; E-mail: jm.rolain{at}medecine.univ-mrs.fr
Objectives: Bartonella bacilliformis is the aetiological agent of Carrion's disease. Although ciprofloxacin, rifampicin and erythromycin have been successfully used in the treatment of the disease, failures and relapses have been reported. The objective of our study was to select in vitro mutants resistant to antibiotics in order to determine the frequency of mutations and to characterize the mechanism of resistance at the molecular level.
Methods: Antibiotic-resistant mutants were selected by serial passages of bacteria on blood agar plates containing antibiotics. Candidate genes involved in resistance were amplified and sequenced and compared in order to look at mutations associated with antibiotic resistance.
Results: Ciprofloxacin-, rifampicin- and erythromycin-resistant mutants were obtained after five, three and four passages, respectively. Conversely, no mutant was obtained with either gentamicin or doxycycline even after 16 passages. The ciprofloxacin mutant contained an amino acid change at position 87 (Asp 
Asn) in its quinolone resistance-determining region of the DNA gyrase protein, whereas the rifampicin-resistant strain had an amino acid change at position 531 (Ser Phe) in the rifampicin resistance-determining region of the rpoB gene. Similarly, the erythromycin-resistant mutant showed an A2058G mutation in the 23S rRNA gene.
Conclusions: According with the current knowledge on the treatment of human bartonellosis, we believe that doxycycline in association with gentamicin may be the preferred regimen for the treatment of the acute and eruptive stages of Carrion's disease, but clinical trials are warranted to support our findings.
Keywords: Carrion's disease , genomic , bioinformatics , in vitro selection , disc diffusion assay
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