Ellington M J, Livermore D M, Pitt T L, Hall L M C, Woodford N
Antibiotic Resistance Monitoring and Reference Laboratory, Centre for Infections, Health Protection Agency, London, UK.
Clin Microbiol Infect. 2006 Aug;12(8):800-3. doi: 10.1111/j.1469-0691.2006.01424.x.
TEM-1 and TEM(pUC19)beta-lactamases can gain activity against ceftazidime and other expanded-spectrum cephalosporins via point mutation. The frequency of emergent resistance to ceftazidime at 4 x MIC was elevated >or= 250-fold in hyper-mutable, MutS-deficient Escherichia coli harbouring these beta-lactamase genes on high- or low-copy plasmids. Moreover, although ceftazidime-resistant mutants, or those with reduced susceptibility, were selected in both the wild-type and mutS hosts, many more mutants in the mutS host showed ceftazidimase-type extended-spectrum beta-lactamase (ESBL) activity. This correlated with a G-A point mutation at position 484 in the bla(TEM-1) and bla(TEM-pUC19) genes, conferring the Arg164His amino-acid substitution found in the TEM-29 ESBL. Non-ESBL mutants lacked changes in bla(TEM).
TEM-1和TEM(pUC19)β-内酰胺酶可通过点突变获得对头孢他啶及其他广谱头孢菌素的活性。在携带这些β-内酰胺酶基因的高拷贝或低拷贝质粒的超突变、MutS缺陷型大肠杆菌中，对4倍最低抑菌浓度（MIC）的头孢他啶出现耐药的频率升高了≥250倍。此外，虽然在野生型和mutS宿主中均筛选出了耐头孢他啶的突变体或敏感性降低的突变体，但mutS宿主中的许多突变体表现出头孢他啶酶型超广谱β-内酰胺酶（ESBL）活性。这与bla(TEM-1)和bla(TEM-pUC19)基因第484位的G-A点突变相关，该突变导致了在TEM-29 ESBL中发现的Arg164His氨基酸替代。非ESBL突变体的bla(TEM)没有变化。
Zotero 插件