Morosini M I, Negri M C, Shoichet B, Baquero M R, Baquero F, Blázquez J
Servicio de Microbiologia, Hospital Ramón y Cajal, Madrid, Spain.
FEMS Microbiol Lett. 1998 Aug 1;165(1):85-90. doi: 10.1111/j.1574-6968.1998.tb13131.x.
A predictive approach was assayed to evaluate the possibility of mutant Amp-C beta-lactamase emergence with increased substrate spectrum (including new C-3' quaternary ammonium cephems). The ampC gene encoding the AmpC beta-lactamase from Enterobacter cloacae was cloned and expressed in an AmpC-defective strain of E. coli. After the AmpC containing strain was challenged with cefpirome, an ampC variant encoding an enzyme with increased resistance to cefpirome and cefepime was selected. In addition, this variant conferred increased resistance to penicillins and third generation cephalosporins. The complete nucleotide sequence of the gene was determined. The deduced peptide sequence showed a single change with respect to the wild-type gene: valine to glutamic acid at position 318 of the native protein (298 of the mature enzyme). The potential emergence and spread of this type of AmpC variants among pathogens should be considered.
采用一种预测方法来评估随着底物谱增加（包括新型C-3'季铵头孢菌素）出现突变型Amp-Cβ-内酰胺酶的可能性。编码阴沟肠杆菌AmpCβ-内酰胺酶的ampC基因被克隆并在大肠杆菌的AmpC缺陷菌株中表达。在用头孢匹罗对含AmpC的菌株进行挑战后，选择了一个编码对头孢匹罗和头孢吡肟耐药性增加的酶的ampC变体。此外，该变体对青霉素和第三代头孢菌素的耐药性也增加。测定了该基因的完整核苷酸序列。推导的肽序列显示与野生型基因有一个单一变化：天然蛋白第318位（成熟酶的第298位）的缬氨酸变为谷氨酸。应考虑这类AmpC变体在病原体中潜在的出现和传播。
