title: Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance.
abstract: The substantial use of antibiotics in the clinic, combined with a dearth of new antibiotic classes, has led to a gradual increase in the resistance of bacterial pathogens to these compounds. Among the various mechanisms by which bacteria endure the action of antibiotics, those affecting influx and efflux are of particular importance, as they limit the interaction of the drug with its intracellular targets and, consequently, its deleterious effects on the cell. This review evaluates the impact of porins and efflux pumps on two major types of resistance, namely, mutational and adaptive types of resistance, both of which are regarded as key phenomena in the global rise of antibiotic resistance among pathogenic microorganisms. In particular, we explain how adaptive and mutational events can dramatically influence the outcome of antibiotic therapy by altering the mechanisms of influx and efflux of antibiotics. The identification of porins and pumps as major resistance markers has opened new possibilities for the development of novel therapeutic strategies directed specifically against these mechanisms.
authors.affiliation: Centre for Microbial Diseases and Immunity Research, Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Lucía
authors.initials: L
authors.lastname: Fernández
authors.forename: Robert E W
authors.initials: RE
authors.lastname: Hancock
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D001419:Bacteria / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D018407:Bacterial Physiological Phenomena; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D018272:Porins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; D018272:Porins