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Open Access Highly Accessed Research article

Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus

Sofia Santos Costa12, Celeste Falcão1, Miguel Viveiros13, Diana Machado14, Marta Martins145, José Melo-Cristino6, Leonard Amaral134 and Isabel Couto12*

Author Affiliations

1 Grupo de Micobactérias, Unidade de Microbiologia Médica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT, UNL), Rua da Junqueira, 100, 1349-008 Lisbon, Portugal

2 Centro de Recursos Microbiológicos (CREM), Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa, Quinta da Torre, 2829-516 Caparica, Portugal

3 COST ACTION BM0701 (ATENS

4 Unidade de Parasitologia e Microbiologia Médica (UPMM), Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa; Rua da Junqueira, 100, 1349-008 Lisbon, Portugal

5 UCD School of Public Health, Physiotherapy and Population Science, UCD Centre for Food Safety, Veterinary Sciences Centre, University College Dublin, Belfield Dublin 4, Ireland

6 Centro Hospitalar Lisboa Norte E.P.E., Instituto de Microbiologia, Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Avenida Professor Egas Moniz, 1649-028 Lisbon, Portugal

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BMC Microbiology 2011, 11:241  doi:10.1186/1471-2180-11-241

Published: 27 October 2011

Abstract

Background

Antimicrobial resistance mediated by efflux systems is still poorly characterized in Staphylococcus aureus, despite the description of several efflux pumps (EPs) for this bacterium. In this work we used several methodologies to characterize the efflux activity of 52 S. aureus isolates resistant to ciprofloxacin collected in a hospital in Lisbon, Portugal, in order to understand the role played by these systems in the resistance to fluoroquinolones.

Results

Augmented efflux activity was detected in 12 out of 52 isolates and correlated with increased resistance to fluoroquinolones. Addition of efflux inhibitors did not result in the full reversion of the fluoroquinolone resistance phenotype, yet it implied a significant decrease in the resistance levels, regardless of the type(s) of mutation(s) found in the quinolone-resistance determining region of grlA and gyrA genes, which accounted for the remaining resistance that was not efflux-mediated. Expression analysis of the genes coding for the main efflux pumps revealed increased expression only in the presence of inducing agents. Moreover, it showed that not only different substrates can trigger expression of different EP genes, but also that the same substrate can promote a variable response, according to its concentration. We also found isolates belonging to the same clonal type that showed different responses towards drug exposure, thus evidencing that highly related clinical isolates may diverge in the efflux-mediated response to noxious agents. The data gathered by real-time fluorometric and RT-qPCR assays suggest that S. aureus clinical isolates may be primed to efflux antimicrobial compounds.

Conclusions

The results obtained in this work do not exclude the importance of mutations in resistance to fluoroquinolones in S. aureus, yet they underline the contribution of efflux systems for the emergence of high-level resistance. All together, the results presented in this study show the potential role played by efflux systems in the development of resistance to fluoroquinolones in clinical isolates of S. aureus.