ABSTRACT
A wide range of prescreening tests for antimicrobial activity of 59 bacterial isolates from sediments of Ria Formosa Lagoon (Algarve, Portugal) disclosed Vibrio spartinae 3.6 as the most active antibacterial producing strain. This bacterial strain, which has not previously been submitted for chemical profiling, was subjected to de novo whole genome sequencing, which aided in the discovery and elucidation of a prodigiosin biosynthetic gene cluster that was predicted by the bioinformatic tool KEGG BlastKoala. Comparative genomics led to the identification of a new membrane di-iron oxygenase-like enzyme, annotated as Vspart_02107, which is likely to be involved in the biosynthesis of cycloprodigiosin and analogues. The combined genomics-metabolomics profiling of the strain led to the isolation and identification of one new branched-chain prodigiosin (5) and to the detection of two new cyclic forms. Furthermore, the evaluation of the minimum inhibitory concentrations disclosed the major prodigiosin as very effective against multi-drug-resistant pathogens including Stenotrophomonas maltophilia, a clinical isolate of Listeria monocytogenes, as well as some human pathogens reported by the World Health Organization as prioritized targets.
Subject(s)
Anti-Bacterial Agents/biosynthesis , Indoles/chemistry , Pyrroles/chemistry , Vibrio/genetics , Vibrio/metabolism , Anti-Bacterial Agents/chemistry , Bacteria/drug effects , Computational Biology , Cyclization , Drug Resistance, Multiple, Bacterial/drug effects , Genomics , Listeria monocytogenes/drug effects , Metabolomics , Microbial Sensitivity Tests , Spectrometry, Mass, Electrospray Ionization , Stenotrophomonas maltophilia/drug effectsABSTRACT
The increasing emergence of new forms of multidrug resistance among human pathogenic bacteria, coupled with the consequent increase of infectious diseases, urgently requires the discovery and development of novel antimicrobial drugs with new modes of action. Most of the antibiotics currently available on the market were obtained from terrestrial organisms or derived semisynthetically from fermentation products. The isolation of microorganisms from previously unexplored habitats may lead to the discovery of lead structures with antibiotic activity. The deep-sea environment is a unique habitat, and deep-sea microorganisms, because of their adaptation to this extreme environment, have the potential to produce novel secondary metabolites with potent biological activities. This review covers novel antibiotics isolated from deep-sea microorganisms. The chemical classes of the compounds, their bioactivities, and the sources of organisms are outlined. Furthermore, the authors report recent advances in techniques and strategies for the exploitation of deep-sea microorganisms.
