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

Abstract

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 Sarcophyton 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 6 th and the 3 rd 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.

Production and characterization of staphylokinase enzyme from Staphylococcus aureus ASIA4

“…They were catalase and methyl red tests positive ( Figure 6). In accordance with our data, previously studies reported that S. aureus isolates grown on blood agar with β-hemolysis activity and on mannitol salt agar medium, which considered a selective and differential medium for S. aureus turned its color from red to yellow as a result of mannitol fermentation and acid production and they are positive for catalase, coagulase and MR-VP tests but negative for indole test [5,[23][24][25]. Also, Shah and Panchal, stated that S. aureus isolates are snowy, creamy to gold color and as Gram positive cocci with β-haemolysis on blood agar and proteolysis on casein agar plates [3].…”

“…the highest microbial growth 7.90 and 7.82 log CFU/mL recorded with fructose and glucose as well as 8.00 and 8.90 log CFU/mL obtained with beef extract and yeast extract but growth values markedly increased with adding amino acid alanine, glycine, histidine and lysine to reach 10.15, 11.93, 10.00 and 11.19 log CFU/mL, respectively. Consistent with literature sources, the optimum temperature for the growth of S. aureus was ranged from 37 to 40 °C as well as beef extract, dextrose and NaCl were reported as the most suitable parameters [18,23,24].…”

“…On the other hand, El-Gendy, et al reported that cancer patients are susceptible to staphylococcal infection owing to a number of reasons comprising prolonged hospitalization and operating time, intravascular catheterization, compromise immunity, malignancy, chemotherapy, radiotherapy and antibiotic therapy [22,23]. Moreover, El-Gendy, et al isolated 468 S. aureus isolates from cancer patients among them 283 were MRSA and El-Gendy, et al isolated 41 clinical S. aureus out of them 73.2% were from El-Demerdash hospital and 26.8% from Ain Shams Specialized hospital [23,24].…”

Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus

“…Most of these compounds were isolated from terrestrial sources (Barka et al, 2016;Van Der Meij et al, 2017). However, there were reports recently, where their marine counterparts were also recognized as a source of bioactive compounds (Shaik et al, 2017;Yang and Song, 2017;El-Gendy et al, 2018;Kemung et al, 2018;Subramani and Sipkema, 2019). The condition in the marine environment is remarkably different from that of the terrestrial environment.…”

Evaluation of the antibacterial and anticancer activities of marine Bacillus subtilis ESRAA3010 against different multidrug resistant Enterococci (MDRE) and cancer cell lines

“…They gain increasing concern due to their facility for withstanding the in luence of various antibacterial agents, accordingly limit the drug of choices and leads to higher mortality and morbidity [4]. Therefore, inding of alternate powerful, inexpensive and harmless natural agents against multidrug resistant bacteria can be potent way for solving this serious global problem [5][6][7]. Marine bacteria are promising reservoirs of diverse effective bioactive natural products and many of them are being used in chemotherapy to treatment human diseases especially with the continuing need for new potent compounds against drug-resistant pathogens and https://doi.org/10.29328/journal.abb.1001018 managing of distressing cancers with high selective activity and less toxicity [8,9].…”