The multiple antibiotic resistance, or mar, gene is a segment of bacterial DNA that enables a bacterium to withstand the effects of various, structurally different antibiotics. This capability presents a substantial challenge in medical fields, as it complicates the treatment of bacterial infections.
The Mar Operon System
The mar gene does not operate in isolation; it is part of a coordinated unit of genes called the marRAB operon. This system functions as a regulated switch for antibiotic resistance. The operon consists of three main parts. The MarR protein it produces acts as a repressor, binding to the DNA and preventing the resistance machinery from turning on when not needed.
Working in opposition to the repressor is the activator component, encoded by the marA gene. The MarA protein functions as the ‘on switch,’ activating a broad network of genes that protect the bacterium. The final component is the marB gene, which is found alongside marR and marA, though its precise function remains less defined but is thought to contribute to the overall resistance phenotype.
This arrangement of a repressor and an activator allows the bacterium to conserve energy, keeping the resistance network dormant until a specific threat is detected. The interplay between MarR and MarA is the operon’s central control point, ensuring the defensive response is deployed only when necessary.
Activation and Mechanism of Resistance
The activation of the mar system is triggered by specific chemical stressors. When substances, including antibiotics like tetracycline and chloramphenicol, or natural compounds such as salicylate, enter the cell, they interact with the MarR repressor protein. This interaction causes the MarR protein to release its grip on the DNA, allowing the marA gene to be expressed.
Once the MarA activator protein is produced, it initiates a two-pronged defensive strategy. The first action is the upregulation of cellular pumps known as efflux pumps. MarA directly activates the genes for building the AcrAB-TolC efflux pump, a protein complex that spans the bacterial cell envelope. This pump functions like a bilge pump on a boat, actively expelling antibiotic molecules from within the cell before they can cause damage.
Simultaneously, MarA reduces the number of entry points for antibiotics by decreasing the production of proteins called porins, specifically a channel known as OmpF. MarA activates a small regulatory RNA molecule called MicF, which binds to the messenger RNA of ompF, preventing it from being translated into a functional porin. This action slows the influx of harmful antibiotic compounds.
Clinical and Environmental Significance
The mar operon is found in many common and clinically important bacteria, including pathogenic strains of Escherichia coli and Salmonella. Its presence in these organisms, frequent causes of foodborne illness and urinary tract infections, poses a challenge to treatment. When the mar system is activated during an infection, it can render standard antibiotic therapies less effective, forcing clinicians to use more potent drugs.
While the resistance conferred by the mar system is often at a low level, it is considered an initial step toward high-level clinical resistance. The operon’s ability to be induced by substances beyond antibiotics, including disinfectants and organic solvents, highlights its role as a general stress-response system. This versatility makes it a survival tool for bacteria in diverse environments like the human gut, soil, and water.