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.
Highlights
The National Institutes of Health (NIH) reported an estimated 17 million infections arising in the U.S each year resulting in half a million fatalities
The sponge samples were identified as Xestospongia testudinaria (01), Halichondria sp. (02), Rhabdastrella globostellata (03), Stelletta sp. (04), Geodia sp. (05), Dysidea sp. (06), Coelocarteria singaporensis (07), Haliclona sp. (08), cf
The findings suggested that the two bacterial strains probably belong to a putatively novel bacterial genus class or that the marine bacteria strains in question were not previously studied in detail
Summary
The National Institutes of Health (NIH) reported an estimated 17 million infections arising in the U.S each year resulting in half a million fatalities. Because this strategy requires no killing of bacterial cells, it is proposed to reduce the occurrence of resistant strains [4] This approach prevents bacterial diseases by attenuating expression of the genes responsible for pathogenicity, such as bacterial attachment, biofilm formation, chemical signaling, evasion of the host immune system, and the secretion of toxins. One such effective strategy proposed is through the interference of pathogenic bacterial quorum sensing systems using natural products [1,5,6,7]. The integration of both metabolomics and genomic techniques employed in this study is an effective and informed decision-making approach for the selection of marine bacterial strains with high probability of discovering novel bioactive compounds
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