Francois Patrice, Tangomo Manuela, Hibbs Jonathan, Bonetti Eve-Julie, Boehme Catharina C, Notomi Tsugunori, Perkins Mark D, Schrenzel Jacques
Genomic Research Laboratory, University Hospitals of Geneva, Service of Infectious Diseases, Geneva, Switzerland.
FEMS Immunol Med Microbiol. 2011 Jun;62(1):41-8. doi: 10.1111/j.1574-695X.2011.00785.x. Epub 2011 Mar 16.
We evaluated the robustness of loop-mediated isothermal amplification (LAMP) of DNA for bacterial diagnostic applications. Salmonella enterica serovar Typhi was used as the target organism and compared with a real-time quantitative PCR (qPCR) for testing assay performance and reproducibly, as well as the impact of pH and temperature stability. This isothermal amplification method appeared to be particularly robust across 2 pH units (7.3-9.3) and temperature values (57-67 °C). The detection limit was comparable to that observed using optimized home-brew qPCR assays. The specificity of the amplification reaction remained high even at temperatures markedly different from the optimal one. Exposing reagents to the ambient temperature during the preparation of the reaction mixture as well as prolonging times for preparing the amplification reaction did not yield false-positive results. LAMP remained sensitive and specific despite the addition of untreated biological fluids such as stool or urine that commonly inhibit PCR amplification. Whereas the detection of microorganisms from whole blood or a blood-culture medium typically requires extensive sample purification and removal of inhibitors, LAMP amplification remained more sensitive than conventional qPCR when omitting such preparatory steps. Our results demonstrate that LAMP is not only easy to use, but is also a very robust, innovative and powerful molecular diagnostic method for both industrialized and developing countries.
我们评估了用于细菌诊断的DNA环介导等温扩增(LAMP)的稳健性。使用伤寒沙门氏菌血清型伤寒杆菌作为目标生物体,并与实时定量PCR(qPCR)进行比较,以测试检测性能、重现性以及pH和温度稳定性的影响。这种等温扩增方法在2个pH单位(7.3 - 9.3)和温度值(57 - 67°C)范围内表现出特别的稳健性。检测限与使用优化的自制qPCR检测方法所观察到的相当。即使在明显不同于最佳温度的条件下,扩增反应的特异性仍然很高。在制备反应混合物期间将试剂暴露于环境温度以及延长扩增反应的制备时间均未产生假阳性结果。尽管添加了通常会抑制PCR扩增的未经处理的生物流体(如粪便或尿液),LAMP仍然保持敏感和特异。虽然从全血或血培养基中检测微生物通常需要广泛的样品纯化和去除抑制剂,但在省略此类制备步骤时,LAMP扩增仍然比传统qPCR更敏感。我们的结果表明,LAMP不仅易于使用,而且对于工业化国家和发展中国家而言,都是一种非常稳健、创新且强大的分子诊断方法。