In vitro selection of fluoroquinolone resistance in Brucella melitensis

Autor: Max Maurin, N. Ravanel, B. Gestin
Přispěvatelé: Université Joseph Fourier - Grenoble 1 (UJF), Laboratoire de Bactériologie, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)
Rok vydání: 2008
Předmět:
DNA Mutational Analysis
Drug resistance
Resistance mechanisms
DNA gyrase
MESH: Membrane Transport Proteins
Moxifloxacin
heterocyclic compounds
Pharmacology (medical)
MESH: DNA Mutational Analysis
Enzyme Inhibitors
MESH: Bacterial Proteins
Antibacterial agent
MESH: Microbial Sensitivity Tests
0303 health sciences
MESH: DNA Topoisomerases
General Medicine
Anti-Bacterial Agents
Infectious Diseases
MESH: Enzyme Inhibitors
Efflux
medicine.drug
Fluoroquinolones
Microbiology (medical)
Tetracycline
Mutation
Missense
Microbial Sensitivity Tests
Biology
Brucellosis
Microbiology
03 medical and health sciences
Minimum inhibitory concentration
Bacterial Proteins
MESH: Anti-Bacterial Agents
MESH: Drug Resistance
Bacterial
Drug Resistance
Bacterial
medicine
Brucella melitensis
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
030304 developmental biology
MESH: Mutation
Missense
030306 microbiology
Membrane Transport Proteins
MESH: Fluoroquinolones
biochemical phenomena
metabolism
and nutrition
bacterial infections and mycoses
biology.organism_classification
Brucella
MESH: Brucella melitensis
DNA Topoisomerases
Zdroj: International Journal of Antimicrobial Agents
International Journal of Antimicrobial Agents, Elsevier, 2009, 34 (1), pp.76. ⟨10.1016/j.ijantimicag.2009.01.002⟩
International Journal of Antimicrobial Agents, Elsevier, 2009, 34 (1), pp.76-81. ⟨10.1016/j.ijantimicag.2009.01.002⟩
ISSN: 1872-7913
0924-8579
Popis: International audience; Moxifloxacin-resistant mutants of Brucella melitensis 16M [moxifloxacin minimum inhibitory concentration (MIC)=1mg/L] were selected in order to characterise fluoroquinolone resistance mechanisms in this species. Eight independent mutants were obtained, with moxifloxacin MICs of 16-32mg/L. The mutants displayed variable cross-resistance levels to other fluoroquinolone compounds, but no increased resistance to aminoglycosides, tetracycline, rifampicin, macrolides or co-trimoxazole. Sequencing of type II topoisomerase-encoding genes (gyrA, gyrB, parC and parE), which are natural targets for fluoroquinolones, revealed a gyrA mutation leading to the amino acid substitution Ala83Val (Escherichia coli numbering system) in five mutants with a moxifloxacin MIC of 32mg/L, whereas no mutation was found in the remaining three mutants with a MIC of 16mg/L. Phenylalanine-arginine-beta-naphthylamide dihydrochloride, an efflux pump inhibitor, reduced moxifloxacin MICs by a factor of two to eight in all resistant mutants. In B. melitensis, fluoroquinolone resistance may arise from gyrA mutation and efflux pump overexpression mechanisms.
Databáze: OpenAIRE
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