Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes Micromonospora sp. UR56 and Actinokinespora sp. EG49.
Mohamed S HifnawyHossam M HassanRabab MohammedMohamed M FoudaAhmed M SayedAhmed Rh AhmedSameh F AbouZidMostafa E RatebHani A AlhadramiUsama Ramadan AbdelmohsenPublished in: Marine drugs (2020)
Liquid chromatography coupled with high resolution mass spectrometry (LC-HRESMS)-assisted metabolomic profiling of two sponge-associated actinomycetes, Micromonospora sp. UR56 and Actinokineospora sp. EG49, revealed that the co-culture of these two actinomycetes induced the accumulation of metabolites that were not traced in their axenic cultures. Dereplication suggested that phenazine-derived compounds were the main induced metabolites. Hence, following large-scale co-fermentation, the major induced metabolites were isolated and structurally characterized as the already known dimethyl phenazine-1,6-dicarboxylate (1), phenazine-1,6-dicarboxylic acid mono methyl ester (phencomycin; 2), phenazine-1-carboxylic acid (tubermycin; 3), N-(2-hydroxyphenyl)-acetamide (9), and p-anisamide (10). Subsequently, the antibacterial, antibiofilm, and cytotoxic properties of these metabolites (1-3, 9, and 10) were determined in vitro. All the tested compounds except 9 showed high to moderate antibacterial and antibiofilm activities, whereas their cytotoxic effects were modest. Testing against Staphylococcus DNA gyrase-B and pyruvate kinase as possible molecular targets together with binding mode studies showed that compounds 1-3 could exert their bacterial inhibitory activities through the inhibition of both enzymes. Moreover, their structural differences, particularly the substitution at C-1 and C-6, played a crucial role in the determination of their inhibitory spectra and potency. In conclusion, the present study highlighted that microbial co-cultivation is an efficient tool for the discovery of new antimicrobial candidates and indicated phenazines as potential lead compounds for further development as antibiotic scaffold.
Keyphrases
- liquid chromatography
- ms ms
- high resolution mass spectrometry
- high glucose
- diabetic rats
- mass spectrometry
- silver nanoparticles
- ultra high performance liquid chromatography
- tandem mass spectrometry
- single cell
- solid phase extraction
- microbial community
- endothelial cells
- escherichia coli
- climate change
- simultaneous determination
- drug induced
- high intensity
- gas chromatography
- cell free
- candida albicans
- biofilm formation
- essential oil
- pseudomonas aeruginosa
- human health