Drug Research Program, Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, FI-00014 Helsinki, Finland.
Int J Mol Sci. 2020 Apr 25;21(9):3034. doi: 10.3390/ijms21093034.
In recent years, bacterial infections have become a main concern following the spread of antimicrobial resistance. In addition, bacterial biofilms are known for their high tolerance to antimicrobials and they are regarded as a main cause of recalcitrant infections in humans. Many efforts have been deployed in order to find new antibacterial therapeutic options and the high-throughput screening (HTS) of large libraries of compounds is one of the utilized strategies. However, HTS efforts for anti-biofilm discovery remain uncommon. Here, we miniaturized a 96-well plate (96WP) screening platform, into a 384-well plate (384WP) format, based on a sequential viability and biomass measurements for the assessment of anti-biofilm activity. During the assay optimization process, different parameters were evaluated while using and as the bacterial models. We compared the performance of the optimized 384WP platform to our previously established 96WP-based platform by carrying out a pilot screening of 100 compounds, followed by the screening of a library of 2000 compounds to identify new repurposed anti-biofilm agents. Our results show that the optimized 384WP platform is well-suited for screening purposes, allowing for the rapid screening of a higher number of compounds in a run in a reliable manner.
近年来，随着抗菌药物耐药性的传播，细菌感染已成为一个主要关注点。此外，细菌生物膜因其对抗菌药物的高耐受性而闻名，被认为是人类顽固性感染的主要原因。为了寻找新的抗菌治疗方法，人们已经做出了许多努力，其中高通量筛选（HTS）大量化合物库是一种被广泛采用的策略。然而，针对抗生物膜的 HTS 工作仍然很少。在这里，我们基于连续的活菌和生物量测量，将 96 孔板（96WP）筛选平台微型化为 384 孔板（384WP）格式，用于评估抗生物膜活性。在优化测定过程中，使用 和 作为细菌模型，评估了不同的参数。我们通过对 100 种化合物进行初步筛选，然后对 2000 种化合物库进行筛选，以确定新的再利用抗生物膜剂，比较了优化的 384WP 平台与我们之前建立的基于 96WP 的平台的性能。我们的结果表明，优化的 384WP 平台非常适合筛选目的，可以可靠地快速筛选更多化合物。
