Adaptive and Mutational Resistance: Role of Porins and Efflux Pumps in Drug Resistance

Abstract

SUMMARY 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.

Novel drug delivery systems to combat antimicrobial resistance

“…Upon extended exposure to antibiotics, bacteria can modify these pumps to efflux antibiotics outside the cell. Thus, even the antibiotic reaches inside the cell by escaping other resistant mechanisms, it can still be actively pumped out [15,18,19].…”

“…Resistance via mutation can be considered one form of adaptive resistance. Additionally, adaptive resistance may also be due to environmentally triggered genetic changes such as nutrient conditions, growth state, subtherapeutic concentrations of antibiotics itself [15], etc. Alternatively, bacteria can also gain resistance from other resistant strains via horizontal gene transfer (HGT) (plasmid, transposons, integrons, etc.)…”

“…Alternatively, bacteria can also gain resistance from other resistant strains via horizontal gene transfer (HGT) (plasmid, transposons, integrons, etc.) during conjugation-"acquired resistance" [15,16].…”

İnsan ve Hayvan Örneklerinden İzole Edilen Escherichia coli’nin İlaç Direnci ve İntegronların Yaygınlığında Antibiyotik Rolü

“…However, over the past decades a rapid increase in the number of antibiotic-resistant clinical isolates has been observed as well as a low rate of development and introduction of new antimicrobial agents have been occurred [5][6][7] .…”

“…However, antibiotic maladministration stabilizes resistance, in other words selection pressure mediated by antibiotics can shift normal micro flora to antibiotic-Role of Antibiotic in Drug ... resistant microorganisms to increase the resistance gene transferring rate [5] .…”