Mechanisms of resistance: useful tool to design antibacterial agents for drug - resistant bacteria

Abstract

Drug-resistant bacteria are now a global health threat. In the last 5 years the WHO, The House of Lords (UK), the Centre for Disease Control (USA) and many more agencies have presented reports on the scale of this problem. Microorganisms multiply very rapidly and have adapted to fill almost every available environmental niche (Rapidly growing species of bacteria under ideal conditions of growth can multiply in about 20 minutes). All members of the chemically related beta-lactam class act at the same phase in cell wall synthesis; as a result, a bacterial cell resistant to one agent is often resistant to all other analogues. The beta-peptide has two promising characteristics that distinguish it from traditional antibiotics. Firstly, bacteria may have trouble developing resistance to the beta-peptide since bacterial defenses may not recognize its unnatural amino acids. Secondly, the magainins that the beta-peptides mimic have been around for millions of years, yet bacteria have not become resistant to them. All classes of antibiotics are subject to resistance by an efflux mechanism mediated by more than one type of pump within the same organism. The bacterial cell may have a membrane pump capable of pumping a class or several classes of antibacterial agents back out of the cell. Other mechanisms of drug resistance include destruction of beta-lactam ring by beta-lactamases, impermeability of the drug into the bacterial cell wall, alteration of targets within the bacterial cells and the by-pass mechanism (bacterial cell may have acquired an alternative mechanism for achieving the essential function).