ABSTRACT
The development and clinical use of antibiotics significantly decreased adverse effects from bacterial infections. In response to the pressure of antibiotics, multiple resistance mechanisms became widespread and are threatening the clinical utility of antibacterial therapy. Bacteria protect themselves from antibiotics by various mechanisms such as enzymatic degradation or modification of antibiotics, modification of antibiotic targets or effluxing antibiotics out of cells. The active efflux of antibiotics as a mechanism of resistance was discovered by S.Levy and coworkers in 1980 when they were studying the mechanism of tetracycline resistance in Enterobacteria (Levy, 1992). Since then, it has been demonstrated that one or multiple efflux pumps participate in the efflux of antibiotics, and resistance to almost all antibiotics could be achieved by extruding them out of cells through these pumps. Some efflux pumps selectively extrude specific antibiotics and some, so-called multidrug resistance (MDR) pumps, efflux varieties of structurally diverse compounds. In this latter case a single protein may confer resistance to multiple antibiotics with different modes of action. Many MDR pumps are normal constituents of bacterial chromosomes and increased antibiotic resistance is a consequence of overexpression of MDR pumps. Thus, bacteria have the potential to develop multidrug resistance without acquisition of multiple specific resistance determinants. Constitutive expres-
sion of some MDR pumps makes bacteria less susceptible to antibiotics.
