Bioactivities and Extract Dereplication of Actinomycetales Isolated From Marine Sponges

Abstract

In the beginning of the twenty-first century, humanity faces great challenges regarding diseases and health-related quality of life. A drastic rise in bacterial antibiotic resistance, in the number of cancer patients, in the obesity epidemics and in chronic diseases due to life expectation extension are some of these challenges. The discovery of novel therapeutics is fundamental and it may come from underexplored environments, like marine habitats, and microbial origin. Actinobacteria are well-known as treasure chests for the discovery of novel natural compounds. In this study, eighteen Actinomycetales isolated from marine sponges of three Erylus genera collected in Portuguese waters were tested for bioactivities with the main goal of isolating and characterizing the responsible bioactive metabolites. The screening comprehended antimicrobial, anti-fungal, anti-parasitic, anti-cancer and anti-obesity properties. Fermentations of the selected strains were prepared using ten different culturing media. Several bioactivities against the fungus Aspergillus fumigatus , the bacteria Staphylococcus aureus methicillin-resistant (MRSA) and the human liver cancer cell line HepG2 were obtained in small volume cultures. Screening in higher volumes showed consistent anti-fungal activity by strain Dermacoccus sp. #91-17 and Micrococcus luteus Berg02-26. Gordonia sp. Berg02-22.2 showed anti-parasitic ( Trypanosoma cruzi ) and anti-cancer activity against several cell lines (melanoma A2058, liver HepG2, colon HT29, breast MCF7 and pancreatic MiaPaca). For the anti-obesity assay, Microbacterium foliorum #91-29 and #91-40 induced lipid reduction on the larvae of zebrafish ( Danio rerio ). Dereplication of the extracts from several bacteria showed the existence of a variety of secondary metabolites, with some undiscovered molecules. This work showed that Actinomycetales are indeed good candidates for drug discovery.

The sponges Hymeniacidon perlevis and Halichondria panicea are reservoirs of antibiotic‐producing bacteria against multi‐drug resistant Staphylococcus aureus

“…Such a percentage of isolates capable of inhibiting the growth of Gram-positive and Gram-negative reference strains is rare. The bulk (87Á0%) of studies on sponge bacteria report a percentage under 15Á0%, half of which are in fact under 5Á0% (Hentschel et al 2001;Zheng et al 2005;Anand et al 2006;Chelossi et al 2007;Marinho et al 2009;Zhang et al 2009;Santos et al 2010Santos et al , 2019Flemer et al 2012;Margassery et al 2012;Papaleo et al 2012;Esteves et al 2013;Haber and Ilan 2014;Grac ßa et al 2015;Laport et al 2017;Matobole et al 2017;Bibi et al 2018Bibi et al , 2020Trianto et al 2019;Freitas-Silva et al 2020;Rajasabapathy et al 2020). Similar results have only been reported in three studies (Kennedy et al 2009;O' Halloran et al 2011;Zeng et al 2013).…”

“…The percentage (70Á2%) of sponge isolates inhibiting the growth of antimicrobial-susceptible S. aureus ATCC 29213 is also remarkable. A review of the literature on the antibacterial activity of sponge bacteria against S. aureus reference strains highlighted that this percentage is much higher than the one obtained in comparable studies, which ranges between 1Á5 and 32Á0% (Hentschel et al 2001;Zheng et al 2005;Chelossi et al 2007;Kennedy et al 2009;Marinho et al 2009;Zhang et al 2009;Santos et al 2010Santos et al , 2019Flemer et al 2012;Margassery et al 2012;Papaleo et al 2012;Xi et al 2012;Esteves et al 2013;Zeng et al 2013;Haber and Ilan 2014;Laport et al 2017;Bibi et al 2018;Trianto et al 2019;Freitas-Silva et al 2020;Rajasabapathy et al 2020). Only one study with a similar percentage of active strains against S. aureus was found (74%), but it exclusively focused on Pseudovibrio isolates (O' Halloran et al 2011).…”

The Marine Seagrass Halophila stipulacea as a Source of Bioactive Metabolites against Obesity and Biofouling

“…Our work evidenced the lipid-reducing activity of some extracts (EL, ML) with EC 50 values of 1.2-2.2 µg/mL using the zebrafish Nile red fat metabolism assay as a whole small animal model in vivo. This assay was used previously to show the lipid-lowering effects of extracts of raw materials or marine organisms (wine lee, actinobacteria, cyanobacteria, sponges), or isolated compounds (polyphenols, chlorophyll derivatives) [19][20][21][22][23]. The original paper from Jones et al [24] demonstrated that zebrafish responded to lipid modulator drugs in the same way as humans.…”

From Ocean to Medicine: Pharmaceutical Applications of Metabolites from Marine Bacteria

“…In fact, this is important not only to help reduce the number of strains to work with, but also to discriminate promising strains belonging to the same species, as even phylogenetically close strains can have different genomic content regarding the presence of biosynthetic gene clusters [ 131 ]. Moreover, this approach has proven to be successful in helping select good candidates which ultimately showed interesting bioactive profiles, including the potential production of novel molecules [ 131 , 132 , 133 ]. Furthermore, with the increase in available data on sequenced bacterial genomes, genome mining techniques have rapidly evolved for detecting secondary metabolite gene clusters [ 134 ].…”