Abstract
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.
Highlights
Due to the misuse and overuse of antibiotics, the emergence of pathogens that are resistant to virtually all of the currently available antibiotics has reached a critical stage
A collection of 72 Pseudovibrio isolates from the marine sponges Axinella dissimilis, Polymastia boletiformis and Haliclona simulans, which were previously classified into 33 groups based on their RAPD profiles [31], was further investigated for antimicrobial activity
In contrast to previous studies, tolerance to Tropodithietic Acid (TDA), which was prevalent among marine sponge isolates, was not associated with native TDA production in these strains
Summary
Due to the misuse and overuse of antibiotics, the emergence of pathogens that are resistant to virtually all of the currently available antibiotics has reached a critical stage For this reason, there has been an urgent drive towards the discovery of new antimicrobial compounds. Sponges rely on an arsenal of metabolites, generally produced by their associated microorganisms, to defend against disease and to gain a competitive advantage within the marine ecosystem [2]. This symbiotic relationship is essential for sponge efficiency and survival [3]. Recent evidence suggests that the majority of bioactive compounds isolated from sponges are likely to be produced by associated microbiota [5]
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