Characterization of <i>Salmonella </i>spp. Mutants with Reduced Fluoroquinolone Susceptibility: Importance of Efflux Pump Mechanisms

Abstract

Background: Westudied the importance of the efflux pump mechanisms in Salmonella spp. mutants with reduced fluoroquinolone susceptibility generated in vitro. Methods: The efflux pump was studied using MC-207,110 as an inhibitor of these systems. Results: Wild strains with mutations in gyrA exhibit greater activity of the efflux pump systems thannalidixic-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. Conclusions: 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.

High Level of Resistance to nalidixic acid in Salmonella enterica serovar Typhi in Central India

“…This phenomenon occludes the use of nalidixic acid resistance determination by the disk diffusion method as a tool to screen for decreased ciprofloxacin susceptibility in non-typhoidal Salmonella. This resistance pattern may possibly be due to the presence of an efflux pump mechanism [12,13] or mutations at locations other than gyrA [11]. Fluoroquinolone resistance in non-typhoidal Salmonella has emerged as a threat to the health community in the past few years [14,15,16]; therefore, invasive infections with serious complication caused by non-typhoidal Salmonella should be treated with increased caution to avoid treatment failures [17].…”

Molecular Epidemiology and Antibiotic Resistance Patterns of <i>Salmonella enterica</i> from Southwestern Greece

“…Reduced susceptibility to fluoroquinolones has been reported to be associated with the activation of efflux pump systems even among strains without gyrA mutations [13] . In another study, testing susceptibility of S .…”

Importance of the Efflux Pump Systems in the Resistance of <i>Mycobacterium tuberculosis</i> to Fluoroquinolones and Linezolid

“…Their usefulness has been repeatedly demonstrated in in vitro assays [1] , in animal models [2] and in the treatment of patients with this disease [3] . However, there have also been reports on the emergence of clinical isolates resistant to these compounds, in many cases associated with mutations in the gyrase (gyr) gene [4,5] , while the efflux pump systems have also been reported to be involved in the resistance to these compounds [6,7] .…”