Barlow Miriam, Hall Barry G
Biology Department, University of Rochester, Rochester, New York 14627, USA.
Antimicrob Agents Chemother. 2002 May;46(5):1190-8. doi: 10.1128/AAC.46.5.1190-1198.2002.
To determine whether the widespread clinical use of beta-lactams has been selective for Citrobacter freundii-derived alleles of plasmid ampC genes, we generated a Bayesian consensus phylogeny of the published ampC sequences and compared the MICs of 16 beta-lactam antibiotics for Escherichia coli strains containing cloned copies of the C. freundii ampC alleles. We found that for the majority of compounds investigated, there has been essentially no increase in beta-lactam resistance conferred by those alleles. We also found that ampC alleles from the chromosomes of two beta-lactam-sensitive C. freundii strains isolated in the 1920s, before the clinical use of antibiotics, were as effective at providing beta-lactam resistance in E. coli as were the plasmid-borne alleles from beta-lactam-resistant clinical isolates. These results suggest that selection for increased resistance to beta-lactam antibiotics has not been a significant force directing the evolution of the C. freundii ampC alleles found in beta-lactam-resistant clinical isolates.
为了确定β-内酰胺类药物在临床上的广泛使用是否对弗氏柠檬酸杆菌来源的质粒ampC基因等位基因具有选择性，我们构建了已发表ampC序列的贝叶斯共识系统发育树，并比较了16种β-内酰胺类抗生素对含有弗氏柠檬酸杆菌ampC等位基因克隆拷贝的大肠杆菌菌株的最低抑菌浓度（MIC）。我们发现，对于大多数所研究的化合物，这些等位基因赋予的β-内酰胺耐药性基本上没有增加。我们还发现，在20世纪20年代抗生素临床使用之前分离出的两株对β-内酰胺敏感的弗氏柠檬酸杆菌菌株染色体上的ampC等位基因，在大肠杆菌中提供β-内酰胺耐药性的效果与来自β-内酰胺耐药临床分离株的质粒携带等位基因相同。这些结果表明，对β-内酰胺类抗生素耐药性增加的选择并不是驱动β-内酰胺耐药临床分离株中弗氏柠檬酸杆菌ampC等位基因进化的重要因素。
