Du Bois S K, Marriott M S, Amyes S G
Department of Medical Microbiology, Medical School, University of Edinburgh, UK.
J Antimicrob Chemother. 1995 Jan;35(1):7-22. doi: 10.1093/jac/35.1.7.
The later-generation cephalosporins were developed to overcome beta-lactamases which conferred resistance to earlier beta-lactam drugs. Within two years of their clinical introduction, the ubiquitous TEM and SHV plasmid-encoded beta-lactamase genes underwent simple point mutations that changed key amino acids around the active site of the protein and enabled the enzyme to bind and hydrolyse these new drugs. Successive mutations interacted in concert, radically increasing the enzymes' abilities to bind and confer resistance to later-generation cephalosporins. These modified enzymes have been classified in three groups, based on activity, and altered functions have been correlated with changes in the enzyme structure.
新一代头孢菌素的研发是为了克服能使早期β-内酰胺类药物产生耐药性的β-内酰胺酶。在其临床应用的两年内，普遍存在的TEM和SHV质粒编码的β-内酰胺酶基因发生了简单的点突变，这些突变改变了蛋白质活性位点周围的关键氨基酸，使该酶能够结合并水解这些新药。连续的突变协同作用，极大地提高了该酶结合并赋予对新一代头孢菌素耐药性的能力。这些修饰后的酶根据活性被分为三组，其功能的改变与酶结构的变化相关。
