Characterization of Salmonella spp. Mutants with Reduced Fluoroquinolone Susceptibility: Importance of Efflux Pump Mechanisms

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Abstract
We studied the importance of the efflux pump mechanisms in Salmonella spp. mutants with reduced fluoroquinolone susceptibility generated in vitro. The efflux pump was studied using MC-207,110 as an inhibitor of these systems. Wild strains with mutations in gyrA exhibit greater activity of the efflux pump systems than nalidixic-acid-susceptible strains (30-fold). When we evaluate the respective mutants, in those of susceptible strains there is seen to be greater elimination of the antibiotic (13-fold), whereas in mutants of nalidixic-acid-resistant strains these systems are not modified. When evaluating the influence of the antibiotic generating the mutants, ciprofloxacin is seen to be the quinolone that activates the efflux pump systems the most. Repeated exposure to low concentrations of all the fluoroquinolones studied leads to activation of the efflux pump systems and a reduction in susceptibility, even when there are no mutations in gyrA. Activation of these mechanisms is greatly influenced by the chemical structure of the antibiotic. The capacity of these systems to eliminate fluoroquinolones is limited and therefore, for the microorganism to acquire high-level fluoroquinolone resistance, they must be complemented by other mechanisms.