The exoskeleton of bacterial cells (the sacculus): still a highly attractive target for antibacterial agents that will last for a long time.
Most bacteria are entirely surrounded by a strong cell wall held together by covalent bonds of strength similar to those holding the atoms in a diamond together. This exoskeleton is a coat of armor or corset and is usually called a sacculus. It protects the bacterium from the stresses resulting from the higher osmotic pressure of the cytoplasm when compared with its environment. This strategy of constructing an external mechanical support has the weakness that the wall barrier has to be cleaved and new wall material inserted outside of the cell proper in order for the bacterium to grow and divide. Because of the unique chemistry and the necessity of selectively cleaving old stress-bearing wall for growth, the wall of the bacterial cell has been a key target for chemotherapeutic treatment of bacterial diseases. Currently, many infectious organisms are becoming resistant to overused antibiotics. Still the wall is a good target, and there could possibly be several entirely new classes of antibiotics targeted toward other parts of wall metabolism and function. The essential autolysins may be a particularly relevant target. To find chemotherapeutic agents we must use and extend our present understanding of the structural mechanics of bacterial wall and their biophysics, biochemistry, and physiology. Moreover, if we use our knowledge of biophysics/genetics and of the evolution of antibiotic resistance mutations that occurred millions of years ago, as well as our knowledge of ones that have arisen recently, quite novel antibiotics may be designed.
Koch
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Biology Department, Indiana University, Bloomington 47405-6801, USA. Koch@Indiana.edu
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001105:Archaea / Q000187:drug effects; D018407:Bacterial Physiological Phenomena / Q000187:drug effects*; D005075:Biological Evolution; D002240:Carbohydrate Sequence; D002473:Cell Wall / Q000187:drug effects*; D004352:Drug Resistance, Microbial; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010457:Peptidoglycan / Q000378:metabolism
D000900:Anti-Bacterial Agents; D010457:Peptidoglycan