[Inhibition of pump and permeability mechanisms]

The presence of multidrug efflux-pump systems in bacteria showing resistance to various drugs is increasingly reported in the literature. These systems are inducible by compounds such as salicylate and can thus be involved in situations of phenotypic resistance at the point of the infection which would otherwise be barely detectable under standard laboratory testing conditions. On the other hand, mutants which overproduce efflux-pumps and show increased levels of antibiotic resistance are easily selectable. It has been shown that inactivation of efflux-pump determinants produces an increased susceptibility to different antibiotics as well as prevents the emergence of mutants with a high-level antibiotic resistance to drugs such as quinolones. The search for efflux-pump inhibitors to be used in combination with other currently used antibiotics is therefore an important task for the renewal of the antibacterial therapeutic armamentarium. No efflux-pump inhibitors are commercially available as yet. However, several companies are in the process of working on their development. In this review, we discuss four possible targets that could be useful in the screening of inhibitors of efflux-pump systems in bacteria.