Enne Virve I, Bennett Peter M, Livermore David M, Hall Lucinda M C
Bristol Centre for Antimicrobial Research, Department of Pathology and Microbiology, University of Bristol, Medical Sciences Building, University Walk, Bristol BS8 1TD.
J Antimicrob Chemother. 2004 Jun;53(6):958-63. doi: 10.1093/jac/dkh217. Epub 2004 Apr 21.
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.
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.
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.
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.
尽管临床磺胺类药物的使用量减少了97%,但在英国,大肠杆菌中磺胺类耐药性的流行率一直保持稳定。磺胺类耐药性与其他耐药性的基因连锁被认为对这种稳定性很重要,但这一发现也意味着磺胺类耐药性几乎没有适应性代价。为了验证这一假设,我们研究了四种天然存在的携带sul2基因的质粒对其宿主的适应性影响。
通过在基本培养基中的成对生长竞争来确定质粒对大肠杆菌的适应性影响。通过引物步移和PCR获得质粒p9123的DNA序列。
所研究的四种携带sul2基因的质粒中有三种对其宿主造成了适应性代价。第四种质粒,一个携带sul2、strA和strB的6.2 kb抗性元件,命名为p9123,对其原始临床宿主以及大肠杆菌K12 JM109都赋予了4%的适应性优势。p9123的完整序列揭示了八个开放阅读框,其中五个功能未知。没有明显的基因可以解释这种适应性优势。
p9123可以提高宿主适应性这一新颖发现,或许可以解释为什么这种质粒及其近亲在肠道细菌中如此广泛存在。除了其他因素,如其他药物对磺胺类耐药性的共同选择外,像p9123这样的质粒所赋予的适应性优势,可能在没有临床选择压力的情况下,对英国磺胺类耐药性的维持起到了作用。这些数据表明,一旦抗生素耐药性在移动遗传元件上确立,可能就难以消除。