Pylkkö Tuomas, Schneider Yannik Karl-Heinz, Rämä Teppo, Andersen Jeanette Hammer, Tammela Päivi
Drug Research Program, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
Marbio, Faculty for Fisheries, Biosciences and Economy, UiT-The Arctic University of Norway, Tromsø, Norway.
Front Microbiol. 2024 Aug 30;15:1432475. doi: 10.3389/fmicb.2024.1432475. eCollection 2024.
A considerable number of antibacterial agents are derived from bacterial metabolites. Similarly, numerous known compounds that impede bacterial virulence stem from bacterial metabolites. Enteropathogenic (EPEC) is a notable human pathogen causing intestinal infections, particularly affecting infant mortality in developing regions. These infections are characterized by microvilli effacement and intestinal epithelial lesions linked with aberrant actin polymerization. This study aimed to identify potential antivirulence compounds for EPEC infections among bacterial metabolites harvested from marine actinobacteria ( sp. and spp.) from the Arctic Sea by the application of virulence-based screening assays. Moreover, we demonstrate the suitability of these antivirulence assays to screen actinobacteria extract fractions for the bioassay-guided identification of metabolites. We discovered a compound in the fifth fraction of a strain that interferes with EPEC-induced actin polymerization without affecting growth. Furthermore, a growth-inhibiting compound was identified in the fifth fraction of a strain. Our findings include the bioassay-guided identification, HPLC-MS-based dereplication, and isolation of a large phospholipid and a likely antimicrobial peptide, demonstrating the usefulness of this approach in screening for compounds capable of inhibiting EPEC virulence.
相当数量的抗菌剂源自细菌代谢产物。同样，许多已知的阻碍细菌毒力的化合物也源于细菌代谢产物。肠致病性大肠杆菌（EPEC）是一种引起肠道感染的重要人类病原体，尤其影响发展中地区的婴儿死亡率。这些感染的特征是微绒毛消失和与异常肌动蛋白聚合相关的肠道上皮病变。本研究旨在通过基于毒力的筛选试验，从北冰洋海洋放线菌（属和种）收获的细菌代谢产物中鉴定出用于EPEC感染的潜在抗毒力化合物。此外，我们证明了这些抗毒力试验适用于筛选放线菌提取物馏分，以进行生物测定指导的代谢产物鉴定。我们在一株菌的第五馏分中发现了一种化合物，它能干扰EPEC诱导的肌动蛋白聚合而不影响生长。此外，在另一株菌的第五馏分中鉴定出一种生长抑制化合物。我们的研究结果包括生物测定指导的鉴定、基于HPLC-MS的去重复以及一种大磷脂和一种可能的抗菌肽的分离，证明了这种方法在筛选能够抑制EPEC毒力的化合物方面的有用性。
