Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49
Liquid chromatography coupled with high resolution mass spectrometry (LC-HRESMS)-assisted metabolomic profiling of two sponge-associated actinomycetes, <i>Micromonospora</i> sp. UR56 and <i>Actinokineospora</i> sp. EG49, revealed that the co-culture of these two actinomycetes...
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MDPI AG
2020-05-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/5/243 |
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| author | Mohamed S. Hifnawy Hossam M. Hassan Rabab Mohammed Mohamed M. Fouda Ahmed M. Sayed Ahmed A. Hamed Sameh F. AbouZid Mostafa E. Rateb Hani A. Alhadrami Usama Ramadan Abdelmohsen |
| author_facet | Mohamed S. Hifnawy Hossam M. Hassan Rabab Mohammed Mohamed M. Fouda Ahmed M. Sayed Ahmed A. Hamed Sameh F. AbouZid Mostafa E. Rateb Hani A. Alhadrami Usama Ramadan Abdelmohsen |
| author_sort | Mohamed S. Hifnawy |
| collection | DOAJ |
| description | Liquid chromatography coupled with high resolution mass spectrometry (LC-HRESMS)-assisted metabolomic profiling of two sponge-associated actinomycetes, <i>Micromonospora</i> sp. UR56 and <i>Actinokineospora</i> 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 (<b>1</b>), phenazine-1,6-dicarboxylic acid mono methyl ester (phencomycin; <b>2</b>), phenazine-1-carboxylic acid (tubermycin; <b>3</b>), N-(2-hydroxyphenyl)-acetamide (<b>9</b>), and <i>p</i>-anisamide (<b>10</b>). Subsequently, the antibacterial, antibiofilm, and cytotoxic properties of these metabolites (<b>1</b>–<b>3</b>, <b>9</b>, and <b>10</b>) 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 <i>Staphylococcus</i> DNA gyrase-B and pyruvate kinase as possible molecular targets together with binding mode studies showed that compounds <b>1</b>–<b>3</b> 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. |
| first_indexed | 2024-03-10T20:01:07Z |
| format | Article |
| id | doaj.art-3607b23116c041aa9b630170ebfc12fd |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T20:01:07Z |
| publishDate | 2020-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-3607b23116c041aa9b630170ebfc12fd2023-11-19T23:32:38ZengMDPI AGMarine Drugs1660-33972020-05-0118524310.3390/md18050243Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49Mohamed S. Hifnawy0Hossam M. Hassan1Rabab Mohammed2Mohamed M. Fouda3Ahmed M. Sayed4Ahmed A. Hamed5Sameh F. AbouZid6Mostafa E. Rateb7Hani A. Alhadrami8Usama Ramadan Abdelmohsen9Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, 11787 Cairo, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Nahda University, 62513 Beni-Suef, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Nahda University, 62513 Beni-Suef, EgyptMicrobial Chemistry Department, National Research Center, 33 El-Buhouth Street, 12622 Giza, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, 62514 Beni-Suef, EgyptSchool of Computing, Engineering & Physical Sciences, University of the West of Scotland, Paisley PA1 2BE, UKDepartment of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmacognosy, Faculty of Pharmacy, Minia University, 61519 Minia, EgyptLiquid chromatography coupled with high resolution mass spectrometry (LC-HRESMS)-assisted metabolomic profiling of two sponge-associated actinomycetes, <i>Micromonospora</i> sp. UR56 and <i>Actinokineospora</i> 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 (<b>1</b>), phenazine-1,6-dicarboxylic acid mono methyl ester (phencomycin; <b>2</b>), phenazine-1-carboxylic acid (tubermycin; <b>3</b>), N-(2-hydroxyphenyl)-acetamide (<b>9</b>), and <i>p</i>-anisamide (<b>10</b>). Subsequently, the antibacterial, antibiofilm, and cytotoxic properties of these metabolites (<b>1</b>–<b>3</b>, <b>9</b>, and <b>10</b>) 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 <i>Staphylococcus</i> DNA gyrase-B and pyruvate kinase as possible molecular targets together with binding mode studies showed that compounds <b>1</b>–<b>3</b> 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.https://www.mdpi.com/1660-3397/18/5/243co-cultivationphenazinesponge-associated actinomycetesantibacterialantibiofilmDNA gyrase |
| spellingShingle | Mohamed S. Hifnawy Hossam M. Hassan Rabab Mohammed Mohamed M. Fouda Ahmed M. Sayed Ahmed A. Hamed Sameh F. AbouZid Mostafa E. Rateb Hani A. Alhadrami Usama Ramadan Abdelmohsen Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49 Marine Drugs co-cultivation phenazine sponge-associated actinomycetes antibacterial antibiofilm DNA gyrase |
| title | Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49 |
| title_full | Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49 |
| title_fullStr | Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49 |
| title_full_unstemmed | Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49 |
| title_short | Induction of Antibacterial Metabolites by Co-Cultivation of Two Red-Sea-Sponge-Associated Actinomycetes <i>Micromonospora</i> sp. UR56 and <i>Actinokinespora</i> sp. EG49 |
| title_sort | induction of antibacterial metabolites by co cultivation of two red sea sponge associated actinomycetes i micromonospora i sp ur56 and i actinokinespora i sp eg49 |
| topic | co-cultivation phenazine sponge-associated actinomycetes antibacterial antibiofilm DNA gyrase |
| url | https://www.mdpi.com/1660-3397/18/5/243 |
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