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).

Insights into the mechanisms of action of host defence peptides from biophysical and structural investigations

“…Furthermore, amphipathic helices have been designed in such a manner to allow the easy control of their membrane alignment. These peptides not only exhibit potent antimicrobial and transfection activities, but their investigation has also provided important insights into mechanistic aspects of their biological functions.The continuously increasing resistance of pathogens against many of the commonly used antibiotics imposes new challenges to human health [1,2]. Possible alternatives can be found by exploring natural resources, and interesting antimicrobial compounds have indeed been discovered in the plant [3,4] and in the animal kingdoms [5,6].…”

“…The continuously increasing resistance of pathogens against many of the commonly used antibiotics imposes new challenges to human health [1,2]. Possible alternatives can be found by exploring natural resources, and interesting antimicrobial compounds have indeed been discovered in the plant [3,4] and in the animal kingdoms [5,6].…”

The Bacterial Lectin FimH, a Target for Drug Discovery – Carbohydrate Inhibitors of Type 1 Fimbriae‐Mediated Bacterial Adhesion

“…[12] Typically, bacterial colonization is accompanied by infectious diseases, and this constitutes a major global health problem. [13] In addition, biofilm formation on medical devices and implants frequently causes complications [14] and significantly contributes to the pathogenesis of implant-related infections.…”

Combined effect of synthetic enterocin CRL35 with cell wall, membrane-acting antibiotics and muranolytic enzymes against Listeria cells

“…Antibiotics have been indiscriminately used, and this has contributed to the rise in antibiotic resistance in a wide range of bacteria, using a variety of resistance mechanisms (Boucher et al. 2009; Savjani et al. 2009).…”