JAC Advance Access originally published online on January 16, 2004
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Journal of Antimicrobial Chemotherapy (2004) 53, 240-246
© 2004 The British Society for Antimicrobial Chemotherapy
Enhancement of antibiotic activity by sub-lethal concentrations of enterocin CRL35
Departamento de Bioquímica de la Nutrición, Instituto Superior de Investigaciones Biológicas (Consejo Nacional de Investigaciones Científicas y TécnicasUniversidad Nacional de Tucumán), and Instituto de Química Biológica Dr. Bernabé Bloj, Chacabuco 461, 4000 San Miguel de Tucumán, Argentina
Received 8 September 2003; returned 10 October 2003; revised 6 November 2003; accepted 17 November 2003
Objective: The aim of this study was to evaluate the interaction of several conventional antibiotics with sub-lethal concentrations of enterocin CRL35, a cationic peptide, on Listeria innocua 7.
Methods: Susceptibility of L. innocua 7 cells to the combination of enterocin CRL35 and non-peptide antibiotics (cefalexin, ampicillin, ciprofloxacin, nalidixic acid, erythromycin, chloramphenicol, vancomycin and tetracycline) was assayed using the broth dilution method and killing curves. Fractional inhibitory concentration (FIC) index was calculated to assess synergy. The transmembrane electrical potential and pH gradient were determined by specific fluorescent probes.
Results: We found positive interactions between the cationic peptide and three conventional antibiotics (tetracycline, erythromycin and chloramphenicol) which are excluded from the cells by efflux pumps dependent on the membrane proton gradient. Furthermore, enterocin CRL35 even at sub-lethal concentrations induced the dissipation of both components of the proton motive force (
p), i.e. transmembrane electrical potential and pH gradient and hence the alteration of processes dependent on it.
Conclusion: We hypothesize that enterocin CRL35 increases the effectiveness of these antibiotics by impairment of the bacterial active efflux systems and the consequent accumulation of these toxic compounds in the cytoplasm.
Keywords: antibiotic, cationic peptides, bacteriocins, multidrug efflux
* Corresponding author. Fax: +54-381-4248025; E-mail: rdmore{at}unt.edu.ar
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