Marine Sediment-Derived Streptomyces Strain Produces Angucycline Antibiotics against Multidrug-Resistant Staphylococcus aureus Harboring SCCmec Type 1 Gene

Abstract

The Philippine archipelago is geographically positioned in the tropics with rich areas of marine biodiversity. Its marine sediments harbor actinomycetes that exhibit antibacterial activity. Screening of actinomycetes isolated from marine sediments collected near the coast of Islas de Gigantes, Iloilo showed one isolate that exhibited high activity against the multidrug-resistant Staphylococcus aureus (MRSA) strain carrying the Staphylococcal Cassette Chromosome mec (SCCmec) type 1 gene, a biomarker for drug resistance. The isolate was identified as Streptomyces sp. strain DSD011 based on its 16s rRNA and protein-coding genes (atpD, recA, rpoB, and trpB) sequences, and was found to be a new species of salt-tolerant marine Streptomyces. Further, the strain harbors both non-ribosomal peptide synthetase (NRPS) and type II polyketide synthase (PKS) in its genome. The targeted chromatographic isolation and chemical investigations by Liquid Chromatography Mass Spectrometry-Time of Flight (LCMS-TOF), tandem mass spectrometry (MS/MS), and Global Natural Product Social molecular networking (GNPS) of the antibiotics produced by the strain, afforded the two polycyclic aromatic polyketide angucycline glycosides, fridamycin A (1) and fridamycin D (2), which are products of type II PKS biosynthesis. Compounds 1 and 2 displayed antibacterial activity against MRSA with minimum inhibitory concentration(MIC) of 500 μg/mL and 62.5 μg/mL, respectively. These results suggest that the underexplored marine sediments near the coast of Islas de Gigantes, Iloilo offer access to undiscovered Streptomyces species that are invaluable sources of antibiotic leads.

Insights into the Variation in Bioactivities of Closely Related Streptomyces Strains from Marine Sediments of the Visayan Sea against ESKAPE and Ovarian Cancer

“…The Streptomyces sp. strain DSD011 T produces angucycline antibiotics fridamycin A and fridamycin D [ 12 ].…”

“…The species of terrestrial bacteria belonging to this family, particularly 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; thus, the secondary metabolites they produce are as variable as their location [ 18 , 19 ].…”

“…In our recent studies, one species of marine sediment-derived Streptomyces produces new anthracycline antibiotics that cause cell membrane damage in multidrug-resistant Staphylococcus aureus [ 11 ]. Further, a salt-tolerant new species of Streptomyces was isolated from marine sediments collected in the Islas de Gigantes group of islands in the northern part of Iloilo, Philippines, producing polycyclic aromatic polyketide angucycline glycosides fridamycin A and fridamycin D [ 12 ]. These angucycline antibiotics have activities against the multidrug-resistant S. aureus strain, harboring a drug-resistant gene SCCmec [ 12 ].…”

“…Further, a salt-tolerant new species of Streptomyces was isolated from marine sediments collected in the Islas de Gigantes group of islands in the northern part of Iloilo, Philippines, producing polycyclic aromatic polyketide angucycline glycosides fridamycin A and fridamycin D [ 12 ]. These angucycline antibiotics have activities against the multidrug-resistant S. aureus strain, harboring a drug-resistant gene SCCmec [ 12 ]. Our findings demonstrate that the marine sediment-derived Streptomyces from the Philippine archipelago is enriched with the potential to produce bioactive compounds and, thus, need further exploration.…”

Biological Control of Pythium aphanidermatum, the Causal Agent of Tomato Root Rot by Two Streptomyces Root Symbionts

“…Streptomyces spp. are known as biological potential resources for producing more than 75% of bioactive substances and secondary metabolites including more than 80% of the world antibiotics [43][44][45][46]. A range of beneficial microorganisms, especially Streptomyces, can colonize plant roots in symbiotic interaction.…”