Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur, 721302, India.
Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Chennai, 603203, India.
Appl Microbiol Biotechnol. 2018 Sep;102(17):7389-7406. doi: 10.1007/s00253-018-9168-1. Epub 2018 Jun 22.
Quorum sensing, the microbial communication system, is gaining importance as a therapeutic target against pathogens. The two key reasons for the rising demand of quorum sensing (QS) inhibitory molecules are low selective pressure to develop resistance by pathogens and possibility of more species-specific effects. Due to complex interactions in a unique niche of live plant tissues, endophytes, as a survival mechanism, potentially produce various bioactive compounds such as QS inhibitors. We report the isolation of an endophytic fungus Kwoniella sp. PY016 from the medicinal plant "Bahera" (Terminalia bellirica), which exhibits substantial quorum sensing inhibition and anti-biofilm activities against the standard test organism, Chromobacterium violaceum. Sugar, sugar alcohol, carboxylic acid, lipid, and phenolic classes of metabolites (predominantly xylitol) are responsible components of the metabolome for the desired bioactivity. A judicious combination of single-factor-at-a-time strategy and artificial neural network modeling combined with genetic algorithm was employed for the selection and optimization of the critical process and medium parameters. Through this newly adopted hybrid model-based optimization, the quorum sensing inhibitory activity of the endophytic metabolome was increased by ~ 30%. This is the first report on optimization of QS inhibitory activity from any fungal endophyte using such a hybrid advanced approach.
群体感应是一种微生物通讯系统，作为一种针对病原体的治疗靶点，其重要性日益凸显。对群体感应（QS）抑制分子的需求不断增加有两个主要原因：病原体产生耐药性的选择压力较低，以及可能产生更具物种特异性的作用。由于内生菌生活在植物组织这一独特小生境中存在着复杂的相互作用，内生菌可能会产生各种生物活性化合物，如 QS 抑制剂，作为一种生存机制。我们从药用植物“巴赫尔”（Terminalia bellirica）中分离出一株内生真菌 Kwoniella sp. PY016，该真菌对标准测试生物，即变色杆菌（Chromobacterium violaceum）具有显著的群体感应抑制和抗生物膜活性。糖、糖醇、羧酸、脂类和酚类代谢物（主要是木糖醇）是具有所需生物活性的代谢物的主要成分。采用单因素策略和人工神经网络建模与遗传算法相结合的方法，对关键工艺和培养基参数进行了选择和优化。通过这种新采用的混合模型优化，内生代谢物的群体感应抑制活性提高了约 30%。这是首次使用这种混合先进方法对任何真菌内生菌的 QS 抑制活性进行优化的报道。
