Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus
The rise of antibiotic resistance (ABR) and the drying up of the pipeline for the development of new antibiotics demands an urgent search for new antibiotic leads. While the majority of clinically available antibiotics were discovered from terrestrial Streptomyces, related species from marine sedime...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-04-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2020.00743/full |
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| author | Melissa June V. Paderog Melissa June V. Paderog Angelica Faith L. Suarez Edna M. Sabido Zhen Jie Low Jonel P. Saludes Jonel P. Saludes Jonel P. Saludes Doralyn S. Dalisay Doralyn S. Dalisay Doralyn S. Dalisay |
| author_facet | Melissa June V. Paderog Melissa June V. Paderog Angelica Faith L. Suarez Edna M. Sabido Zhen Jie Low Jonel P. Saludes Jonel P. Saludes Jonel P. Saludes Doralyn S. Dalisay Doralyn S. Dalisay Doralyn S. Dalisay |
| author_sort | Melissa June V. Paderog |
| collection | DOAJ |
| description | The rise of antibiotic resistance (ABR) and the drying up of the pipeline for the development of new antibiotics demands an urgent search for new antibiotic leads. While the majority of clinically available antibiotics were discovered from terrestrial Streptomyces, related species from marine sediments as a source of antibiotics remain underexplored. Here, we utilized culture-dependent isolation of thirty-five marine sediment-derived actinobacterial isolates followed by a screening of their antibacterial activity against multidrug-resistant S. aureus ATCC BAA-44. Our results revealed that the crude extract of Streptomyces griseorubens strain DSD069 isolated from marine sediments collected in Romblon, Philippines displays the highest antibacterial activity, with 96.4% growth inhibition. The S. aureus ATCC BAA-44 cells treated with crude extract of Streptomyces griseorubens strain DSD069 showed cell membrane damage as demonstrated by (a) leakage and loss of vital cell constituents, including DNA and proteins, (b) irregular shrinkage of cells, and (c) increase membrane permeability. The antibiotic compounds were identified as Bisanhydroaklavinone and 1-Hydroxybisanhydroaklavinone with MIC value of 6.25 μg/mL and 50.00 μg/mL, respectively. Bisanhydroaklavinone and 1-Hydroxybisanhydroaklavinone are shunt metabolites in the biosynthesis of anticancer anthracycline derivatives namely doxorubicin, daunorubicin, and cinerubins. It is rare, however, that shunt metabolites are accumulated during fermentation of marine sediment-derived Streptomyces strain without genetic modification. Thus, our study provides evidence that natural bacterial strain can produce Bisanhydroaklavinone and 1-Hydroxybisanhydroaklavinone as antibiotic leads to combat ABR. |
| first_indexed | 2024-04-13T14:11:39Z |
| format | Article |
| id | doaj.art-043d6495901e4d7c89ab1850cf41e20a |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-13T14:11:39Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Microbiology |
| spelling | doaj.art-043d6495901e4d7c89ab1850cf41e20a2022-12-22T02:43:46ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-04-011110.3389/fmicb.2020.00743526959Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureusMelissa June V. Paderog0Melissa June V. Paderog1Angelica Faith L. Suarez2Edna M. Sabido3Zhen Jie Low4Jonel P. Saludes5Jonel P. Saludes6Jonel P. Saludes7Doralyn S. Dalisay8Doralyn S. Dalisay9Doralyn S. Dalisay10Department of Pharmacy, College of Health and Allied Medical Professions, University of San Agustin, Iloilo City, PhilippinesCenter for Chemical Biology and Biotechnology (C2B2), University of San Agustin, Iloilo City, PhilippinesCenter for Natural Drug Discovery and Development (CND3), University of San Agustin, Iloilo City, PhilippinesCenter for Natural Drug Discovery and Development (CND3), University of San Agustin, Iloilo City, PhilippinesWaters Pacific Pte Ltd, Singapore, SingaporeCenter for Natural Drug Discovery and Development (CND3), University of San Agustin, Iloilo City, PhilippinesDepartment of Chemistry, College of Liberal Arts, Sciences, and Education, University of San Agustin, Iloilo City, PhilippinesBalik Scientist Program, Philippine Council for Health Research and Development, Department of Science and Technology, Taguig, PhilippinesCenter for Chemical Biology and Biotechnology (C2B2), University of San Agustin, Iloilo City, PhilippinesBalik Scientist Program, Philippine Council for Health Research and Development, Department of Science and Technology, Taguig, PhilippinesDepartment of Biology, College of Liberal Arts, Sciences, and Education, University of San Agustin, Iloilo City, PhilippinesThe rise of antibiotic resistance (ABR) and the drying up of the pipeline for the development of new antibiotics demands an urgent search for new antibiotic leads. While the majority of clinically available antibiotics were discovered from terrestrial Streptomyces, related species from marine sediments as a source of antibiotics remain underexplored. Here, we utilized culture-dependent isolation of thirty-five marine sediment-derived actinobacterial isolates followed by a screening of their antibacterial activity against multidrug-resistant S. aureus ATCC BAA-44. Our results revealed that the crude extract of Streptomyces griseorubens strain DSD069 isolated from marine sediments collected in Romblon, Philippines displays the highest antibacterial activity, with 96.4% growth inhibition. The S. aureus ATCC BAA-44 cells treated with crude extract of Streptomyces griseorubens strain DSD069 showed cell membrane damage as demonstrated by (a) leakage and loss of vital cell constituents, including DNA and proteins, (b) irregular shrinkage of cells, and (c) increase membrane permeability. The antibiotic compounds were identified as Bisanhydroaklavinone and 1-Hydroxybisanhydroaklavinone with MIC value of 6.25 μg/mL and 50.00 μg/mL, respectively. Bisanhydroaklavinone and 1-Hydroxybisanhydroaklavinone are shunt metabolites in the biosynthesis of anticancer anthracycline derivatives namely doxorubicin, daunorubicin, and cinerubins. It is rare, however, that shunt metabolites are accumulated during fermentation of marine sediment-derived Streptomyces strain without genetic modification. Thus, our study provides evidence that natural bacterial strain can produce Bisanhydroaklavinone and 1-Hydroxybisanhydroaklavinone as antibiotic leads to combat ABR.https://www.frontiersin.org/article/10.3389/fmicb.2020.00743/fullantibacterialPhilippine marine sedimentsanthracyclines shunt metabolitesmultidrug-resistant Staphylococcus aureus (MDRSA)Streptomycescell membrane integrity |
| spellingShingle | Melissa June V. Paderog Melissa June V. Paderog Angelica Faith L. Suarez Edna M. Sabido Zhen Jie Low Jonel P. Saludes Jonel P. Saludes Jonel P. Saludes Doralyn S. Dalisay Doralyn S. Dalisay Doralyn S. Dalisay Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus Frontiers in Microbiology antibacterial Philippine marine sediments anthracyclines shunt metabolites multidrug-resistant Staphylococcus aureus (MDRSA) Streptomyces cell membrane integrity |
| title | Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus |
| title_full | Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus |
| title_fullStr | Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus |
| title_full_unstemmed | Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus |
| title_short | Anthracycline Shunt Metabolites From Philippine Marine Sediment-Derived Streptomyces Destroy Cell Membrane Integrity of Multidrug-Resistant Staphylococcus aureus |
| title_sort | anthracycline shunt metabolites from philippine marine sediment derived streptomyces destroy cell membrane integrity of multidrug resistant staphylococcus aureus |
| topic | antibacterial Philippine marine sediments anthracyclines shunt metabolites multidrug-resistant Staphylococcus aureus (MDRSA) Streptomyces cell membrane integrity |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2020.00743/full |
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