In some persistent bacterial infections, bacteria generally grow very slowly or are dormant. In this case, traditional antibiotic drugs that target bacterial biosynthesis are difficult to play a therapeutic role. To solve this problem, Creative Biolabs provides customers with a new solution, which is to achieve the purpose of treatment by destroying the double layer of the bacterial membrane or disturbing the membrane function in the dormant bacteria. The clinical application of this method can refer to lipoglycopeptides that destroy bacterial membranes and diarylquinolines that inhibit membrane-bound ATP synthase. Although there are still some shortcomings, the application of membrane-active agents is an important means to eliminate chronic bacterial infections.
Regardless of the metabolic state of the bacteria, the existence of the cell membrane is essential for its survival. It provides a selective barrier for the stability of bacterial cells and the conduction of energy and matter. In addition, the membrane also contains about a third of the proteins in the cell and is involved in many important physiological processes. Antibacterial peptides (AMP) produced by some hosts and several bioactive molecules acting on the membrane demonstrate their potential as antibacterial targets. But because of concerns that similar compounds could damage mammalian plasma membranes, traditional antibacterial drug screening efforts have not used bacterial cell membranes as targets for antibiotic development.
In recent years, with the successful medical application of membrane-active antibiotics such as daptomycin, telavancin, oritavancin, and dalbavancin, antibacterial drugs targeting cell membranes have been shown to establish bacterial specificity. The key mechanism is that bacterial cell membranes are rich in negatively charged phospholipids (phosphatidylglycerol and cardiolipin) and zwitterionic phosphatidylethanolamine, which can be bound by compounds with a positive charge. For example, daptomycin can oligomerize into a micelle-like amphiphilic structure in the presence of calcium ions, providing a surface with a false positive charge, thereby increasing its affinity for negative ions. In addition, binding to peptidoglycan precursors and bacterial membrane proteins on the membrane also contributes to the specificity of daptomycin and lipoglycopeptides.
Fig.1 Bacterial cell membrane structure. (Epand, 2016)
Creative Biolabs believes that membrane actives can be a promising treatment for chronic bacterial infections. To this end, we can help customers develop antibacterial drugs that target bacterial cell membranes. Our services have the following advantages:
If you are interested in our antimicrobial development services, please contact us for more details.
Reference
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