Enhancement of host fitness by the sul2-coding plasmid p9123 in the absence of selective pressure

Enhancement of host fitness by the sul2-coding plasmid p9123 in the absence of selective pressure
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DOI:
10.1093/jac/dkh217
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发表时间:
2004-06-01
影响因子:
5.2
通讯作者:
Hall, LMC
Hall, LMC
中科院分区:
医学2区
文献类型:
--
作者:
Enne, VI;Bennett, PM;Hall, LMC

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目的:尽管磺胺的临床使用减少了97%,但在英国,大肠杆菌中磺胺耐药性的流行率保持不变。磺胺抗性与其他抗性的遗传联系被认为对这种维持很重要,但这一发现也意味着磺胺抗性产生的适应度成本很小。为了验证这一假设,我们研究了四种自然产生的硫编码质粒对宿主的适应性影响。方法:在最小培养基中,采用两两竞争法测定质粒对大肠杆菌的适合度影响。通过引物行走和PCR得到质粒p9123的DNA序列。结果:研究的四个硫编码质粒中有三个对其宿主施加了适应性成本。第四个质粒是一个6.2 kb的抗性元件,携带sul2、strA和strB,命名为p9123,对其原始临床宿主和大肠杆菌K12 JM109具有4%的适应度优势。p9123完整序列显示8个开放阅读框,其中5个功能未知。没有明显的基因可归因于适合度优势。结论:p9123可以改善宿主适应性的新发现可能解释了为什么这种质粒及其近亲在肠道细菌中如此普遍。除了其他因素,如其他药物对磺胺耐药性的共同选择,在没有临床选择压力的情况下,质粒(如p9123)赋予的适应度优势可能有助于英国磺胺耐药性的维持。这些数据表明,一旦在可移动的遗传元素上建立抗生素耐药性,可能很难消除。
Objectives: Despite a 97% reduction in clinical sulphonamide usage, the prevalence of sulphonamide resistance among Escherichia coli has remained constant in the UK. Genetic linkage of sulphonamide resistance to other resistances is thought important for this maintenance, but the finding also implies that sulphonamide resistance exerts little fitness cost. To test this hypothesis, we examined the fitness impact of four naturally occurring sul2-coding plasmids upon their hosts.Methods: The fitness impact of the plasmids upon E. coli was determined by pairwise growth competition in a minimal medium. The DNA sequence of plasmid p9123 was obtained by primer walking and PCR.Results: Three of the four sul2-coding plasmids studied imposed fitness costs on their hosts. The fourth plasmid, a 6.2 kb resistance element carrying sul2, strA and strB designated p9123, conferred a 4% fitness advantage upon its original clinical host and also on E. coli K12 JM109. The complete sequence of p9123 revealed eight open reading frames, including five of unknown function. There was no obvious gene to which the fitness advantage might be attributed.Conclusions: The novel finding that p9123 can improve host fitness may explain why this plasmid and its close relatives are so widespread among enteric bacteria. In addition to other factors such as co-selection of sulphonamide resistance by other agents, the fitness advantage conferred by plasmids such as p9123 may have contributed to the maintenance of sulphonamide resistance in the UK in the absence of clinical selection pressure. These data indicate that once antibiotic resistance has been established on mobile genetic elements, it may be difficult to eliminate.