Genotypic-Phenotypic Discrepancies between Antibiotic Resistance Characteristics of Escherichia coli Isolates from Calves in Management Settings with High and Low Antibiotic Use

Genotypic-Phenotypic Discrepancies between Antibiotic Resistance Characteristics of Escherichia coli Isolates from Calves in Management Settings with High and Low Antibiotic Use
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DOI:
10.1128/aem.02588-10
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发表时间:
2011-05-01
影响因子:
4.4
通讯作者:
Call, Douglas R.
Call, Douglas R.
中科院分区:
生物学2区
文献类型:
--
作者:
Davis, Margaret A.;Besser, Thomas E.;Call, Douglas R.

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我们假设,在没有抗生素的情况下生长的细菌种群将比在抗生素存在下生长的细菌种群积累更多的耐药基因突变。如果是这样的话,功能失调的耐药基因(耐药假基因)的流行率可以提供一个衡量给定环境中抗生素暴露水平的指标。作为概念验证试验,我们使用耐药基因微阵列检测了大肠杆菌的耐药基因型,并进一步表征了具有耐药表型-基因型差异的菌株。我们发现一个小的,但显着的关联与耐药假基因和较低的抗生素使用环境的肉牛小牛操作与较高的抗生素使用奶牛小牛牧场(Fisher精确检验,P = 0.044)。其他重要的发现包括奶牛场分离株和表型之间的非常强的关联,而这种关联无法用已知的耐药基因来解释(Fisher精确检验,P < 0.0001)。在E.大肠杆菌分离物从乳牛牧场,一个与耐氨基糖苷类和耐甲氧苄啶。此外,对广谱头孢菌素耐药但bla(CMY-2)阴性的分离株在染色体E的启动子区有突变。大肠杆菌ampC基因与报道的天然AmpC β-内酰胺酶过表达一致。在E医院也有类似的突变。大肠杆菌分离株已在世界范围内报道。E.大肠杆菌ampC启动子突变可用作高广谱头孢菌素使用环境的标记。
We hypothesized that bacterial populations growing in the absence of antibiotics will accumulate more resistance gene mutations than bacterial populations growing in the presence of antibiotics. If this is so, the prevalence of dysfunctional resistance genes (resistance pseudogenes) could provide a measure of the level of antibiotic exposure present in a given environment. As a proof-of-concept test, we assayed field strains of Escherichia coli for their resistance genotypes using a resistance gene microarray and further characterized isolates that had resistance phenotype-genotype discrepancies. We found a small but significant association between the prevalence of isolates with resistance pseudogenes and the lower antibiotic use environment of a beef cow-calf operation versus a higher antibiotic use dairy calf ranch (Fisher's exact test, P = 0.044). Other significant findings include a very strong association between the dairy calf ranch isolates and phenotypes unexplained by well-known resistance genes (Fisher's exact test, P < 0.0001). Two novel resistance genes were discovered in E. coli isolates from the dairy calf ranch, one associated with resistance to aminoglycosides and one associated with resistance to trimethoprim. In addition, isolates resistant to expanded-spectrum cephalosporins but negative for bla(CMY-2) had mutations in the promoter regions of the chromosomal E. coli ampC gene consistent with reported overexpression of native AmpC beta-lactamase. Similar mutations in hospital E. coli isolates have been reported worldwide. Prevalence or rates of E. coli ampC promoter mutations may be used as a marker for high expanded-spectrum cephalosporin use environments.