Harrington Catriona, Reen F Jerry, Mooij Marlies J, Stewart Fiona A, Chabot Jean-Baptiste, Guerra Antonio F, Glöckner Frank O, Nielsen Kristian F, Gram Lone, Dobson Alan D W, Adams Claire, O'Gara Fergal
BIOMERIT Research Centre, School of Microbiology, University College Cork-National University of Ireland, Cork, Ireland.
Microbial Genomics and Bioinformatics Research Group, Max Planck Institute for Marine Microbiology, Bremen D-28359, Germany.
Mar Drugs. 2014 Dec 10;12(12):5960-78. doi: 10.3390/md12125960.
The search for new antimicrobial compounds has gained added momentum in recent years, paralleled by the exponential rise in resistance to most known classes of current antibiotics. While modifications of existing drugs have brought some limited clinical success, there remains a critical need for new classes of antimicrobial compound to which key clinical pathogens will be naive. This has provided the context and impetus to marine biodiscovery programmes that seek to isolate and characterize new activities from the aquatic ecosystem. One new antibiotic to emerge from these initiatives is the antibacterial compound tropodithietic acid (TDA). The aim of this study was to provide insight into the bioactivity of and the factors governing the production of TDA in marine Pseudovibrio isolates from a collection of marine sponges. The TDA produced by these Pseudovibrio isolates exhibited potent antimicrobial activity against a broad spectrum of clinical pathogens, while TDA tolerance was frequent in non-TDA producing marine isolates. Comparative genomics analysis suggested a high degree of conservation among the tda biosynthetic clusters while expression studies revealed coordinated regulation of TDA synthesis upon transition from log to stationary phase growth, which was not induced by TDA itself or by the presence of the C10-acyl homoserine lactone quorum sensing signal molecule.
近年来，寻找新型抗菌化合物的工作有了新的动力，与此同时，对大多数已知现有抗生素类别的耐药性呈指数级上升。虽然对现有药物的改良取得了一些有限的临床成功，但仍然迫切需要新型抗菌化合物，以使关键临床病原体对其尚无抗性。这为海洋生物发现计划提供了背景和动力，这些计划旨在从水生生态系统中分离和鉴定新的活性物质。这些计划中出现的一种新型抗生素是抗菌化合物 tropodithietic acid（TDA）。本研究的目的是深入了解从一系列海洋海绵中分离出的海洋假单胞菌菌株中TDA的生物活性以及控制其产生的因素。这些假单胞菌菌株产生的TDA对多种临床病原体表现出强大的抗菌活性，而在不产生TDA的海洋分离株中，对TDA的耐受性很常见。比较基因组学分析表明tda生物合成簇之间具有高度保守性，而表达研究表明，从对数生长期过渡到稳定期生长时，TDA合成受到协调调控，这不是由TDA本身或C10-酰基高丝氨酸内酯群体感应信号分子的存在所诱导的。
