Bush K
Squibb Institute for Medical Research, Princeton, New Jersey 08543-4000.
Rev Infect Dis. 1988 Jul-Aug;10(4):681-90. doi: 10.1093/clinids/10.4.681.
beta-Lactamases, major determinants of bacterial resistance to beta-lactam antibiotics, can be classified into specific molecular classes following identification of active-site amino acid or nucleotide sequences. The use of gene probes for epidemiologic purposes is becoming commoner. A semiempirical classification scheme has been proposed using substrate profiles and inhibition by clavulanic acid and aztreonam as criteria. Class 1 cephalosporinases are potently inhibited by aztreonam but poorly inhibited by clavulanate, whereas class 2 penicillinases and broad-spectrum beta-lactamases have very poor affinities for aztreonam but are inhibited by clavulanic acid. Class 3 beta-lactamases include the metalloenzymes. Resistance to beta-lactam antibiotics can be related to many beta-lactamase-mediated phenomena, including increased frequency of beta-lactamase production in clinical isolates, wider distribution of beta-lactamase-mediating plasmids, production of multiple beta-lactamases, induction of chromosomal class 1 cephalosporinases, selection of depressed mutants for production of class 1 enzymes, leakage of beta-lactamase from gram-negative organisms, functions of penicillin-binding proteins as beta-lactamases, and identification of novel beta-lactamases.
β-内酰胺酶是细菌对β-内酰胺类抗生素耐药的主要决定因素，在确定活性位点氨基酸或核苷酸序列后，可分为特定的分子类别。用于流行病学目的的基因探针的使用正变得越来越普遍。已提出一种半经验分类方案，以底物谱以及克拉维酸和氨曲南的抑制作用作为标准。1类头孢菌素酶被氨曲南强烈抑制，但被克拉维酸盐抑制较弱，而2类青霉素酶和广谱β-内酰胺酶对氨曲南的亲和力非常低，但被克拉维酸抑制。3类β-内酰胺酶包括金属酶。对β-内酰胺类抗生素的耐药性可能与许多β-内酰胺酶介导的现象有关，包括临床分离株中β-内酰胺酶产生频率增加、β-内酰胺酶介导的质粒分布更广泛、多种β-内酰胺酶的产生、染色体1类头孢菌素酶的诱导、产生1类酶的低表达突变体的选择、β-内酰胺酶从革兰氏阴性菌的泄漏、青霉素结合蛋白作为β-内酰胺酶的功能以及新型β-内酰胺酶的鉴定。
