Neu H C
Department of Medicine, Columbia Presbyterian Medical Center, New York, New York 10032.
Diagn Microbiol Infect Dis. 1989 Jul-Aug;12(4 Suppl):109S-116S. doi: 10.1016/0732-8893(89)90122-3.
Many antimicrobial agents have been either found in nature or synthesized in the past 45 years. Antibacterial agents inhibit cell-wall formation, disrupt cytoplasmic membrane function, prevent DNA synthesis, interfere with protein synthesis, and halt folate synthesis. Resistance to antibiotics is a result of three major mechanisms: prevention of the antibacterial agent from reaching its receptor site, production of altered targets, and destruction or modification of the agents. Bacterial resistance has occurred due to chromosomal changes or the presence of plasmids and transposons. Resistance to beta-lactams is the result of beta-lactamases and the production of altered penicillin-binding proteins as well as altered cell-wall permeability. Important examples of these resistance forms occur in staphylococci and pneumococci which have altered penicillin-binding proteins. A new form of target change has been the production of proteins in enterococci that inhibit the activity of glycopeptides. Beta-lactamases are present in both Gram-positive and Gram-negative species; recently, new plasmid beta-lactamases have been isolated that destroy iminomethoxy and iminocarboxy cephalosporins. Resistance to aminoglycosides is due to enzymes that acetylate, adenylate, or phosphorylate aminoglycosides that inhibit binding to ribosomes and thus cause the poor uptake of drug. Tetracycline resistance is due to plasmids which cause efflux of the agent from the cytoplasm. Macrolide and lincinoid resistance is the result of an altered 23S ribosomal component of the 50S ribosomes. Sulfonamide and trimethoprim resistance is due to production of altered synthetase and reductase enzymes essential in the synthesis of folate.(ABSTRACT TRUNCATED AT 250 WORDS)
在过去45年里，人们发现了许多天然存在或合成的抗菌剂。抗菌剂可抑制细胞壁形成、破坏细胞质膜功能、阻止DNA合成、干扰蛋白质合成并停止叶酸合成。抗生素耐药性是由三种主要机制导致的：阻止抗菌剂到达其受体部位、产生改变的靶点以及破坏或修饰抗菌剂。细菌耐药性的产生是由于染色体变化或质粒及转座子的存在。对β-内酰胺类药物的耐药性是由β-内酰胺酶、青霉素结合蛋白的改变以及细胞壁通透性的改变导致的。这些耐药形式的重要例子发生在葡萄球菌和肺炎球菌中，它们的青霉素结合蛋白发生了改变。一种新的靶点变化形式是肠球菌中产生抑制糖肽活性的蛋白质。β-内酰胺酶存在于革兰氏阳性菌和革兰氏阴性菌中；最近，已分离出破坏亚胺甲氧基和亚胺羧基头孢菌素的新型质粒β-内酰胺酶。对氨基糖苷类药物的耐药性是由于使氨基糖苷类药物乙酰化、腺苷酸化或磷酸化的酶，这些酶抑制与核糖体的结合，从而导致药物摄取不良。四环素耐药性是由导致药物从细胞质中流出的质粒引起的。大环内酯类和林可酰胺类耐药性是50S核糖体的23S核糖体成分改变的结果。磺胺类和甲氧苄啶耐药性是由于叶酸合成中必需的合成酶和还原酶发生改变所致。（摘要截选至250词）
