Integrated Genomic and Metabolomic Approach to the Discovery of Potential Anti-Quorum Sensing Natural Products from Microbes Associated with Marine Samples from Singapore

Abstract

With 70% of the Earth’s surface covered in water, the marine ecosystem offers immense opportunities for drug discovery and development. Due to the decreasing rate of novel natural product discovery from terrestrial sources in recent years, many researchers are beginning to look seaward for breakthroughs in new therapeutic agents. As part of an ongoing marine drug discovery programme in Singapore, an integrated approach of combining metabolomic and genomic techniques were initiated for uncovering novel anti-quorum sensing molecules from bacteria associated with subtidal samples collected in the Singapore Strait. Based on the culture-dependent method, a total of 102 marine bacteria strains were isolated and the identities of selected strains were established based on their 16S rRNA gene sequences. About 5% of the marine bacterial organic extracts showed quorum sensing inhibitory (QSI) activity in a dose-dependent manner based on the Pseudomonas aeruginosa QS reporter system. In addition, the extracts were subjected to mass spectrometry-based molecular networking and the genome of selected strains were analysed for known as well as new biosynthetic gene clusters. This study revealed that using integrated techniques, coupled with biological assays, can provide an effective and rapid prioritization of marine bacterial strains for downstream large-scale culturing for the purpose of isolation and structural elucidation of novel bioactive compounds.

Widespread Existence of Quorum Sensing Inhibitors in Marine Bacteria: Potential Drugs to Combat Pathogens with Novel Strategies

“…Screening from various marine environments using either biosensor strains or metagenomic sequencing showed abundance of QS-inhibitory marine bacteria (Figure 1) [30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49]. It could be seen that QS-inhibitory marine bacteria were mainly screened out from sea waters, marine sediments, as well as marine invertebrates, fish, algae, etc.…”

“…Based on screening, many researches have isolated one or several QS-inhibitory bacteria strains from marine origins. The identified bacteria, which have potential QS inhibition ability but have not been further explored for specific QSIs, were categorized in Figure 2 [33,34,35,37,38,40,41,42,43,44,46,47,48,49,50,51,52,53,54,55]. Statistically, QS-inhibitory bacteria could be divided into four phylums and five classes.…”

Linking biosynthetic and chemical space to accelerate microbial secondary metabolite discovery

“…For example, using an integrated approach of combining metabolomic and genomic techniques, Ong and co-workers identified novel metabolites with anti-quorum sensing activity from five bacterial strains isolated from subtidal marine samples (Ong et al . 2019). Their work is a good example of the application of molecular networking-based dereplication in the discovery of secondary metabolites.…”

Draft Genome Sequence of Bacillus sp. Strain 007/AIA-02/001, Isolated from the Marine Sponge Coelocarteria singaporensis

“…Microbes isolated from marine-derived samples, such as marine invertebrates and sediments, are known to produce structurally novel bioactive compounds with significant therapeutic activities, such as anticancer, antifungal, antibiotic, and quorum sensing inhibitory properties (1–5). As such, the marine habitats are a tremendous resource for the discovery of novel drug leads in drug discovery and development efforts (6).…”