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β-Lactams against the Fortress of the Gram-Positive Staphylococcus aureus Bacterium
Chemical Reviews ( IF 62.1 ) Pub Date : 2020-12-29 , DOI: 10.1021/acs.chemrev.0c01010
Jed F Fisher 1 , Shahriar Mobashery 1
Affiliation  

The biological diversity of the unicellular bacteria—whether assessed by shape, food, metabolism, or ecological niche—surely rivals (if not exceeds) that of the multicellular eukaryotes. The relationship between bacteria whose ecological niche is the eukaryote, and the eukaryote, is often symbiosis or stasis. Some bacteria, however, seek advantage in this relationship. One of the most successful—to the disadvantage of the eukaryote—is the small (less than 1 μm diameter) and nearly spherical Staphylococcus aureus bacterium. For decades, successful clinical control of its infection has been accomplished using β-lactam antibiotics such as the penicillins and the cephalosporins. Over these same decades S. aureus has perfected resistance mechanisms against these antibiotics, which are then countered by new generations of β-lactam structure. This review addresses the current breadth of biochemical and microbiological efforts to preserve the future of the β-lactam antibiotics through a better understanding of how S. aureus protects the enzyme targets of the β-lactams, the penicillin-binding proteins. The penicillin-binding proteins are essential enzyme catalysts for the biosynthesis of the cell wall, and understanding how this cell wall is integrated into the protective cell envelope of the bacterium may identify new antibacterials and new adjuvants that preserve the efficacy of the β-lactams.

中文翻译:

β-内酰胺类对抗革兰氏阳性金黄色葡萄球菌的堡垒

单细胞细菌的生物多样性——无论是通过形状、食物、新陈代谢还是生态位来评估——肯定可以与多细胞真核生物相媲美(如果不能超过的话)。生态位是真核生物的细菌与真核生物之间的关系通常是共生或停滞。然而,一些细菌在这种关系中寻求优势。最成功的一种(对真核生物不利)是小(直径小于 1 微米)且接近球形的金黄色葡萄球菌细菌。几十年来,使用青霉素和头孢菌素等β-内酰胺类抗生素成功地临床控制了其感染。在同样的几十年里,金黄色葡萄球菌已经完善了对这些抗生素的耐药机制,然后被新一代的 β-内酰胺结构对抗。本综述通过更好地了解金黄色葡萄球菌如何保护 β-内酰胺类的酶靶点(青霉素结合蛋白),探讨了当前为保护 β-内酰胺类抗生素的未来而开展的生物化学和微生物学工作的广度。青霉素结合蛋白是细胞壁生物合成必不可少的酶催化剂,了解这种细胞壁如何整合到细菌的保护性细胞包膜中,可以识别出新的抗菌剂和新的佐剂,以保持 β-内酰胺的功效。
更新日期:2020-12-29
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