Abstract

Multidrug resistance (MDR) to antibiotics presents a serious therapeutic problem in the treatment of bacterial infections. The importance of this mechanism of resistance in clinical settings is reflected in the increasing number of reports of multidrug resistant isolates. In Salmonella enterica, the most common etiological agent of food borne salmonellosis worldwide, MDR is becoming a major concern. In Salmonella the main mechanisms of antibiotic resistance are mutations in target genes (such as DNA gyrase and topoisomerase IV) and the over-expression of efflux pumps. However, other mechanisms such as changes in the cell envelope; down regulation of membrane porins; increased lipopolysaccharide (LPS) component of the outer cell membrane; quorum sensing and biofilm formation can also contribute to the resistance seen in this microorganism. To overcome this problem new therapeutic approaches are urgently needed. In the case of efflux-mediated multidrug resistant isolates, one of the treatment options could be the use of efflux pump inhibitors (EPIs) in combination with the antibiotics to which the bacteria is resistant. By blocking the efflux pumps resistance is partly or wholly reversed, allowing antibiotics showing no activity against the MDR strains to be used to treat these infections. Compounds that show potential as an EPI are therefore of interest, as well as new strategies to target the efflux systems. Quorum sensing (QS) and biofilm formation are systems also known to be involved in antibiotic resistance. Consequently, compounds that can disrupt or inhibit these bacterial “communication systems” will be of use in the treatment of these infections.

Keywords: Antibiotic resistance, Biofilm formation, Efflux-pumps, Efflux pump inhibitors, Fluoroquinolones, Quorum sensing, Multidrug resistance, DNA gyrase, topoisomerase IV, lipopolysaccharide, Salmonella, lactamases, aminoglycoside, macrolides, Gram-negative bacteria, P-glycoprotein, Multidrug And Toxic compound Extrusion (MATE), Adenosine Triphosphate, (ATP)-Binding Cassette, tribarrel protein, quinolone drugs, tetracycline, chloramphenicol, bile salts, sodium dodecyl sulfate, ethidium bromide, cetyltrimethylammonium bromide, autoinducers, azithromycin, exopolysaccharide, flagellar biosynthesis, AcrB transporter, EtBr assay, benastatins, arylpiperidines, arylpiperazines, phenylalanyl arginyl-naphthylamide, carbonyl cyanide-m chlorophenylhydrazone, Enterobacteriaceae, chemotherapy, Phenyl-arginine-naphthylamide, Proton motive force, Salmonella pathogenicity island-1