Department of Chemistry and Biochemistry, McCourtney Hall, University of Notre Dame, Notre Dame Indiana 46556, United States.
Chem Rev. 2021 Mar 24;121(6):3412-3463. doi: 10.1021/acs.chemrev.0c01010. Epub 2020 Dec 29.
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 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 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 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.
单细胞细菌的生物多样性——无论是从形状、食物、代谢还是生态位来评估——肯定与多细胞真核生物不相上下（如果不是超过的话）。其生态位为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，有些细菌在这种关系中寻求优势。其中一种最成功的细菌——对真核生物不利的细菌——是一种小（直径小于 1 μm）且近乎球形的细菌。几十年来，使用青霉素类和头孢菌素类等β-内酰胺抗生素成功地控制了其感染的临床症状。在这几十年中，它完善了对抗生素的耐药机制，而这些抗生素又被新一代的β-内酰胺结构所对抗。本综述通过更好地了解 如何保护β-内酰胺抗生素的酶靶标——青霉素结合蛋白，来探讨当前在生化和微生物学方面为保护β-内酰胺类抗生素的未来所做的广泛努力。青霉素结合蛋白是细胞壁生物合成的必需酶催化剂，了解细胞壁如何整合到细菌的保护性细胞包膜中，可能会发现新的抗菌药物和新的佐剂，从而保持β-内酰胺类抗生素的疗效。
