Therapy Analysis - Antibiotic-resistance: fighting the superbugs
How do they do it?
Since the introduction of antibiotics, bacteria have developed numerous mechanisms of resistance to antibiotics. In clinical environments such as hospitals, intensive use of antibiotics means there is high potential for bacteria to acquire antibiotic resistance. Under such circumstances, multi-resistant strains of bacteria are relatively common, and give rise to common resistant nosocomial infections such as MRSA, C. diff, and VRE. Several common resistance mechanisms have been identified. Many antibiotics work by inhibiting a key bacterial protein. Bacteria may mutate, deleting the target protein, thereby rendering the antibiotic ineffective. Alternatively, mutation of the target protein may inhibit binding of the antibiotic, preventing its action. Trimethoprim resistance occurs by such a mechanism, and is mediated by alterations in the target enzyme, dihydrofolate reductase (DHFR). Similarly, a mutation in the topoisomerase enzyme, DNA gyrase, is responsible for resistance to quinolone antibiotics such as ciprofloxacin. Target modification also plays a part in antibiotic resistance. In addition to ß-lactamases, MRSA commonly produces an additional penicillin binding protein, PBP2. This binding protein is not susceptible to inhibition by penicillin.
Another mechanism of resistance is evolution of efflux pumps. In certain cases, efflux pumps actively expel the antibiotic from the bacterial cell, confering resistance. This is common in tetracycline-resistant Gram negative bacteria, whereby a pglycoprotein- mediated efflux pump is employed to remove the antibiotic from the bacterium. Another important resistance mechanism involves acetylation of the antibiotic, causing inactivation. This is seen in chloramphenicol resistance.
