Department of Microbiology and Antimicrobial Resistance, Veterinary Research Institute, Brno, Czech Republic.
Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Sci Rep. 2022 Mar 19;12(1):4769. doi: 10.1038/s41598-022-08634-x.
Mycobacterium avium subsp. paratuberculosis (MAP) is a pathogenic bacterium causing the paratuberculosis, chronic and infectious disease common particularly in wild and domestic ruminants. Currently, culture techniques to detect viable MAP are still used most commonly, although these require a long incubation period. Consequently, a faster molecular method for assessing MAP cell viability based on cell membrane integrity was introduced consisting of sample treatment with the intercalation dye propidium monoazide (PMA) followed by quantitative PCR (qPCR). However, the PMA-qPCR assay is complicated by demanding procedures involving work in a darkroom and on ice. In this study, we therefore optimized a viability assay combining sample treatment with palladium (Pd) compounds as an alternative viability marker to PMA, which does not require such laborious procedures, with subsequent qPCR. The optimized Pd-qPCR conditions consisting of 90 min exposure to 30 µM bis(benzonitrile)dichloropalladium(II) or 30 µM palladium(II)acetate at 5 °C and using ultrapure water as a resuspension medium resulted in differences in quantification cycle (Cq) values between treated live and dead MAP cells of 8.5 and 7.9, respectively, corresponding to approximately 2.5 log units. In addition, Pd-qPCR proved to be superior to PMA-qPCR in distinguishing between live and dead MAP cells. The Pd-qPCR viability assay thus has the potential to replace time-consuming culture methods and demanding PMA-qPCR in the detection and quantification of viable MAP cells with possible application in food, feed, clinical and environmental samples.
鸟分枝杆菌亚种副结核(MAP)是一种致病细菌,可引起副结核病,是一种常见的慢性和传染性疾病,尤其在野生和家养反刍动物中。目前,检测有活力的 MAP 的培养技术仍然是最常用的,尽管这些技术需要很长的孵育期。因此,引入了一种更快的基于细胞膜完整性的评估 MAP 细胞活力的分子方法,该方法包括用嵌入染料吖啶橙单叠氮化物(PMA)处理样品,然后进行定量 PCR(qPCR)。然而,PMA-qPCR 测定法很复杂,需要在暗室和冰上进行繁琐的程序。在这项研究中,我们因此优化了一种活力测定法,该方法将样品处理与钯(Pd)化合物结合使用,作为替代 PMA 的活力标记物,而无需进行如此繁琐的程序,随后进行 qPCR。优化的 Pd-qPCR 条件包括在 5°C 下暴露于 30 µM 双(苯腈)二氯化钯(II)或 30 µM 醋酸钯 90 分钟,并使用超纯水作为重悬介质,导致处理后的活和死 MAP 细胞的定量循环(Cq)值分别相差 8.5 和 7.9,分别对应大约 2.5 个对数单位。此外,Pd-qPCR 在区分活和死 MAP 细胞方面优于 PMA-qPCR。因此,Pd-qPCR 活力测定法有可能取代耗时的培养方法和苛刻的 PMA-qPCR,用于检测和定量有活力的 MAP 细胞,可能应用于食品、饲料、临床和环境样本。