Händel Nadine, Otte Sarah, Jonker Martijs, Brul Stanley, ter Kuile Benno H
Dept. of Molecular Biology & Microbial Food Safety, University of Amsterdam, Swammerdam Institute of Life Sciences, Amsterdam, The Netherlands.
MicroArray Department and Integrative Bioinformatics Unit, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, The Netherlands.
PLoS One. 2015 Apr 1;10(4):e0123039. doi: 10.1371/journal.pone.0123039. eCollection 2015.
The spread of antibiotic resistant bacteria worldwide presents a major health threat to human health care that results in therapy failure and increasing costs. The transfer of resistance conferring plasmids by conjugation is a major route by which resistance genes disseminate at the intra- and interspecies level. High similarities between resistance genes identified in foodborne and hospital-acquired pathogens suggest transmission of resistance conferring and transferrable mobile elements through the food chain, either as part of intact strains, or through transfer of plasmids from foodborne to human strains. To study the factors that affect the rate of plasmid transfer, the transmission of an extended-spectrum β-lactamase (ESBL) plasmid from a foodborne Escherichia coli strain to the β-lactam sensitive E. coli MG1655 strain was documented as a function of simulated environmental factors. The foodborne E. coli isolate used as donor carried a CTX-M-1 harboring IncI1 plasmid that confers resistance to β-lactam antibiotics. Cell density, energy availability and growth rate were identified as factors that affect plasmid transfer efficiency. Transfer rates were highest in the absence of the antibiotic, with almost every acceptor cell picking up the plasmid. Raising the antibiotic concentrations above the minimum inhibitory concentration (MIC) resulted in reduced transfer rates, but also selected for the plasmid carrying donor and recombinant strains. Based on the mutational pattern of transconjugant cells, a common mechanism is proposed which compensates for fitness costs due to plasmid carriage by reducing other cell functions. Reducing potential fitness costs due to maintenance and expression of the plasmid could contribute to persistence of resistance genes in the environment even without antibiotic pressure. Taken together, the results identify factors that drive the spread and persistence of resistance conferring plasmids in natural isolates and shows how these can contribute to transmission of resistance genes through the food chain.
全球范围内抗生素耐药菌的传播对人类医疗保健构成了重大健康威胁，导致治疗失败和成本增加。通过接合作用转移赋予耐药性的质粒是耐药基因在种内和种间传播的主要途径。在食源性病原体和医院获得性病原菌中鉴定出的耐药基因高度相似，这表明赋予耐药性且可转移的移动元件通过食物链进行传播，要么作为完整菌株的一部分，要么通过质粒从食源性病原体转移到人类菌株。为了研究影响质粒转移速率的因素，记录了一种超广谱β-内酰胺酶（ESBL）质粒从食源大肠杆菌菌株转移到β-内酰胺敏感的大肠杆菌MG1655菌株的过程，并将其作为模拟环境因素的函数。用作供体的食源大肠杆菌分离株携带一个含有IncI1质粒的CTX-M-1，该质粒赋予对β-内酰胺抗生素的耐药性。细胞密度、能量可用性和生长速率被确定为影响质粒转移效率的因素。在不存在抗生素的情况下转移速率最高，几乎每个受体细胞都能获得质粒。将抗生素浓度提高到最低抑菌浓度（MIC）以上会导致转移速率降低，但也会筛选出携带质粒的供体和重组菌株。基于转接合子细胞的突变模式，提出了一种共同机制来补偿由于携带质粒而导致的适应性成本，即通过减少其他细胞功能来实现。即使在没有抗生素压力的情况下，降低由于质粒维持和表达而产生的潜在适应性成本也可能有助于耐药基因在环境中持续存在。综上所述，这些结果确定了驱动赋予耐药性质粒在自然分离株中传播和持续存在的因素，并展示了它们如何促进耐药基因通过食物链传播。
