Abstract
Marine sediments host diverse actinomycetes that serve as a source of new natural products to combat infectious diseases and cancer. Here, we report the biodiversity, bioactivities against ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) and ovarian cancer, and metabolites variation among culturable actinomycetes isolated from the marine sediments of Visayan Sea, Philippines. We identified 15 Streptomyces species based on a 16S rRNA gene sequence analysis. The crude extracts of 10 Streptomyces species have inhibited the growth of ESKAPE pathogens with minimum inhibitory concentration (MIC) values ranging from 0.312 mg/mL to 20 mg/mL depending on the strain and pathogens targeted. Additionally, ten crude extracts have antiproliferative activity against A2780 human ovarian carcinoma at 2 mg/mL. To highlight, we observed that four phylogenetically identical Streptomyces albogriseolus strains demonstrated variation in antibiotic and anticancer activities. These strains harbored type I and II polyketide synthase (PKS) and non-ribosomal synthetase (NRPS) genes in their genomes, implying that their bioactivity is independent of the polymerase chain reaction (PCR)-detected bio-synthetic gene clusters (BGCs) in this study. Metabolite profiling revealed that the taxonomically identical strains produced core and strain-specific metabolites. Thus, the chemical diversity among these strains influences the variation observed in their biological activities. This study expanded our knowledge on the potential of marine-derived Streptomyces residing from the unexplored regions of the Visayan Sea as a source of small molecules against ESKAPE pathogens and cancer. It also highlights that Streptomyces species strains produce unique strain-specific secondary metabolites; thus, offering new chemical space for natural product discovery.
Highlights
The dramatic increase in incidence of multidrug-resistant (MDR) bacterial infections has only recently stirred the revival of antimicrobial drug discovery programs because of the urgent need to combat emergent life-threatening bacterial infections from “ESKAPE” pathogens, namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. [1]
The low number of isolated streptomycete isolates using ISP4 medium suggests that the use of other isolation media such as noble agar [11] and other isolation marine media with trehalose, raffinose, or mannitol as carbon source [13] are likely to result in the isolation of additional cultivable streptomycetes from the Visayan Seas
We investigated the marine sediment-derived Streptomyces isolates for their potential to produce secondary metabolites by detecting the presence of biosynthetic gene cluster domains through polymerase chain reaction (PCR)-based screening targeting polyketide synthase type I and type II, and for non-ribosomal peptide synthetase (NRPS)
Summary
The dramatic increase in incidence of multidrug-resistant (MDR) bacterial infections has only recently stirred the revival of antimicrobial drug discovery programs because of the urgent need to combat emergent life-threatening bacterial infections from “ESKAPE” pathogens, namely, Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. [1]. The species of terrestrial bacteria belonging to this family, the genus Streptomyces, have been demonstrated to prolifically produce diverse bioactive compounds currently sold in the market and prescribed for clinical use [4,7,8,9]. These free-living, saprophytic microorganisms could be found in diverse environments such as rain forests, lake and ocean sediments, estuaries, as well as deep ocean trenches, lake mud, beach sands, and sponges [5,10,11,12,13,14,15,16,17]. Actinomycetes are adaptive to their environment; the secondary metabolites they produce are as variable as their location [18,19]
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