发布者:抗性基因网 时间:2018-05-28 浏览量:1004
目标:通过转导对临床分离株之间的抗菌药耐药性(AMR)基因进行水平基因转移尚不清楚。 MRSA是机会主义病原体,对所有类别的抗微生物制剂都有抗药性,但目前没有菌株是完全耐药的。金黄色葡萄球菌分离株之间的AMR基因转移主要归因于通过内源性噬菌体的广义转导,并且最近的研究表明转移在宿主定殖期间升高。目的是调查暴露于亚MIC浓度的抗微生物剂是否触发噬菌体诱导和/或提高AMR基因转移的效率。
方法:将来自MRSA携带者的分离物暴露于9种抗微生物剂,并比较溶解噬菌体颗粒的上清液和转移AMR基因的能力。使用新技术,微滴数字PCR来测量噬菌体颗粒中基因的浓度。
结果:所有测试的抗生素均诱导裂解噬菌体和AMR基因转导,尽管转导颗粒与裂解颗粒的比例对于每种抗生素大不相同。莫匹罗星诱导最高比例的转导与裂解颗粒。庆大霉素和新生霉素减少UV诱导的AMR转导。噬菌体颗粒中携带的基因与AMR转移或裂解颗粒活性相关,表明抗微生物剂影响哪些DNA序列被包装到噬菌体颗粒中。
结论:亚抑制性抗生素可诱导临床MRSA之间的AMR基因转移,而联合使用抑制性抗生素可能会将AMR基因包装成噬菌体颗粒,从而减少AMR转移。在不断变化的环境中,如果病原体可以转移DNA而降低裂解性死亡的风险,则病原体具有优势。
Objectives: Horizontal gene transfer of antimicrobial resistance (AMR) genes between clinical isolates via transduction is poorly understood. MRSA are opportunistic pathogens resistant to all classes of antimicrobial agents but currently no strains are fully drug resistant. AMR gene transfer betweenStaphylococcus aureus isolates is predominantly due to generalized transduction via endogenous bacteriophage, and recent studies have suggested transfer is elevated during host colonization. The aim was to investigate whether exposure to sub-MIC concentrations of antimicrobials triggers bacteriophage induction and/or increased efficiency of AMR gene transfer.
Methods: Isolates from MRSA carriers were exposed to nine antimicrobials and supernatants were compared for lytic phage particles and ability to transfer an AMR gene. A new technology, droplet digital PCR, was used to measure the concentration of genes in phage particles.
Results: All antibiotics tested induced lytic phage and AMR gene transduction, although the ratio of transducing particles to lytic particles differed substantially for each antibiotic. Mupirocin induced the highest ratio of transducing versus lytic particles. Gentamicin and novobiocin reduced UV-induced AMR transduction. The genes carried in phage particles correlated with AMR transfer or lytic particle activity, suggesting antimicrobials influence which DNA sequences are packaged into phage particles.
Conclusions: Sub-inhibitory antibiotics induce AMR gene transfer between clinical MRSA, while combination therapy with an inhibiting antibiotic could potentially alter AMR gene packaging into phage particles, reducing AMR transfer. In a continually evolving environment, pathogens have an advantage if they can transfer DNA while lowering the risk of lytic death.
https://academic.oup.com/jac/article/72/6/1624/3076247