Production of bioactive metabolites from different marine endophytic Streptomyces species and testing them against methicillin-resistant Staphylococcus aureus (MRSA) and cancer cell lines

The aim of the work was to identify Actinomycetes strains that are able to produce high levels of anti-MRSA metabolites with a potential use in curing resistant Staphylococcus aureus infections. Twenty-six endophytic Actinomycetes strains were isolated from various marine invertebrates living in two different marine ecosystems (the Mediterranean Sea and the Red Sea). Among them, Streptomyces sp. RS-9 (obtained from the soft coral Sarcophytons sp. from the Red Sea) and Streptomyces sp. MS-26 (obtained from the jellyfish derived from the Mediterranean Sea) demonstrated the highest antagonistic activity against 18 isolates of methicillin-resistant Staphylococcus aureus (MRSA) and 2 isolates of methicillin-resistant coagulase-negative Staphylococci (MRCoNS). The optimization of culture conditions, which includes the time course (at the 6th and the 3rd day of growth), the incubation temperature (27.5EC), pH (8.0 and 6.0), nutritional requirements comprising different metals, carbon (glucose and glycerol, respectively), and nitrogen (mixture of valine with peanut and a mixture of soybean with methionine and asparagines, respectively) sources for RS-9 and MS-26 strains, respectively, resulted in a 2.2-fold and 2.5-fold increase in the productivity of anti-MRSA metabolites. The GC/MS analysis proved the presence of different bioactive compounds in Streptomyces sp. RS-9 and Streptomyces sp. MS-26 extracts. Two pure compounds, A) 1-Methyl-2-acetyl-6-acetoxy-7-methoxy-(1,2,3,4-tetrahydroisoquinoline) and B) -4-(dimethylamino)- 1,4,4d,5,12,12a-hexahydro-3,10,11,12a-tetrahydroxy-6-methyl-1,12-dioxo-,[4S-(4-α,4a,al]–(2-naphthacene carboxamide, which is a well-known antibiotic called anhydrotetracycline), were isolated from Streptomyces sp. MS-26. Those compounds possessed potent anti-MRSA activity against all the tested clinical MRSA and MRCoNS isolates. The minimum inhibition concentration (MIC) of the above two compounds ranged from 16 to 1024 μgml^-1 and 4 to 128 μgml^-1, respectively. The minimum bactericidal concentration (MBC) ranged from 16 to 1024 μgml^-1 and 8 to 128 μgml^-1, respectively with anticancer activity against colon cancer (HCT-16), liver cancer (HepG-2), and lung cancer (A-549) cell lines.