Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity
Abstract Background The search for novel antimicrobial agents is crucial as antibiotic-resistant pathogens continue to emerge, rendering the available antibiotics no longer effective. Likewise, new anti-cancer drugs are needed to combat the emergence of multi-drug resistant tumors. Marine environmen...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-06-01
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| Series: | Microbial Cell Factories |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12934-022-01835-z |
| _version_ | 1828732692823277568 |
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| author | Laila Ziko Omnia AbdelRaheem Marina Nabil Ramy K. Aziz Rania Siam |
| author_facet | Laila Ziko Omnia AbdelRaheem Marina Nabil Ramy K. Aziz Rania Siam |
| author_sort | Laila Ziko |
| collection | DOAJ |
| description | Abstract Background The search for novel antimicrobial agents is crucial as antibiotic-resistant pathogens continue to emerge, rendering the available antibiotics no longer effective. Likewise, new anti-cancer drugs are needed to combat the emergence of multi-drug resistant tumors. Marine environments are wealthy sources for natural products. Additionally, extreme marine environments are interesting niches to search for bioactive natural compounds. In the current study, a fosmid library of metagenomic DNA isolated from Atlantis II Deep Lower Convective Layer (ATII LCL), was functionally screened for antibacterial activity as well as anticancer effects. Results Two clones exhibited antibacterial effects against the marine Bacillus Cc6 strain, namely clones 102-5A and 88-1G and they were further tested against eleven other challenging strains, including six safe relatives of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), a safe relative to Mycobacterium tuberculosis and four resistant clinical isolates. Clone 88-1G resulted in clear zones of inhibition against eight bacterial strains, while clone 102-5A resulted in zones of inhibition against five bacterial strains. The whole cell lysates of clone 88-1G showed 15% inhibition of Mtb ClpP protease -Mycobacterium tuberculosis drug target-, while whole cell lysates of clone 102-5A showed 19% inhibition of Mtb ClpP protease. Whole cell lysates from the selected clones exhibited anticancer effects against MCF-7 breast cancer cells (cell viability at 50% v/v was 46.2% ± 9.9 for 88-1G clone and 38% ± 7 for 102-5A clone), U2OS osteosarcoma cells (cell viability at 50% v/v was 64.6% ± 12.3 for 88-1G clone and 28.3% ± 1.7 for 102-5A clone) and 1BR hTERT human fibroblast cells (cell viability at 50% v/v was 74.4% ± 5.6 for 88-1G clone and 57.6% ± 8.9 for 102-5A clone). Sequencing of 102-5A and 88-1G clones, and further annotation detected putative proteases and putative biosynthetic genes in clones 102-5A and 88-1G, respectively. Conclusions The ATII LCL metagenome hosts putative peptidases and biosynthetic genes that confer antibiotic and anti-cancer effects. The tested clones exhibited promising antibacterial activities against safe relative strains to ESKAPE pathogens and Mycobacterium tuberculosis. Thus, searching the microbial dark matter of extreme environments is a promising approach to identify new molecules with pharmaceutical potential use. |
| first_indexed | 2024-04-12T18:05:39Z |
| format | Article |
| id | doaj.art-c88dc1d0b2d24ba583d84bfc30db2035 |
| institution | Directory Open Access Journal |
| issn | 1475-2859 |
| language | English |
| last_indexed | 2024-04-12T18:05:39Z |
| publishDate | 2022-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbial Cell Factories |
| spelling | doaj.art-c88dc1d0b2d24ba583d84bfc30db20352022-12-22T03:22:00ZengBMCMicrobial Cell Factories1475-28592022-06-0121111310.1186/s12934-022-01835-zBioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activityLaila Ziko0Omnia AbdelRaheem1Marina Nabil2Ramy K. Aziz3Rania Siam4School of Life and Medical Sciences, University of Hertfordshire, Hosted by Global Academic FoundationGraduate Program of Biotechnology, School of Sciences and Engineering, The American University in CairoGraduate Program of Biotechnology, School of Sciences and Engineering, The American University in CairoDepartment of Microbiology and Immunology, Faculty of Pharmacy, Cairo UniversityDepartment of Biology, School of Sciences and Engineering, The American University in CairoAbstract Background The search for novel antimicrobial agents is crucial as antibiotic-resistant pathogens continue to emerge, rendering the available antibiotics no longer effective. Likewise, new anti-cancer drugs are needed to combat the emergence of multi-drug resistant tumors. Marine environments are wealthy sources for natural products. Additionally, extreme marine environments are interesting niches to search for bioactive natural compounds. In the current study, a fosmid library of metagenomic DNA isolated from Atlantis II Deep Lower Convective Layer (ATII LCL), was functionally screened for antibacterial activity as well as anticancer effects. Results Two clones exhibited antibacterial effects against the marine Bacillus Cc6 strain, namely clones 102-5A and 88-1G and they were further tested against eleven other challenging strains, including six safe relatives of ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.), a safe relative to Mycobacterium tuberculosis and four resistant clinical isolates. Clone 88-1G resulted in clear zones of inhibition against eight bacterial strains, while clone 102-5A resulted in zones of inhibition against five bacterial strains. The whole cell lysates of clone 88-1G showed 15% inhibition of Mtb ClpP protease -Mycobacterium tuberculosis drug target-, while whole cell lysates of clone 102-5A showed 19% inhibition of Mtb ClpP protease. Whole cell lysates from the selected clones exhibited anticancer effects against MCF-7 breast cancer cells (cell viability at 50% v/v was 46.2% ± 9.9 for 88-1G clone and 38% ± 7 for 102-5A clone), U2OS osteosarcoma cells (cell viability at 50% v/v was 64.6% ± 12.3 for 88-1G clone and 28.3% ± 1.7 for 102-5A clone) and 1BR hTERT human fibroblast cells (cell viability at 50% v/v was 74.4% ± 5.6 for 88-1G clone and 57.6% ± 8.9 for 102-5A clone). Sequencing of 102-5A and 88-1G clones, and further annotation detected putative proteases and putative biosynthetic genes in clones 102-5A and 88-1G, respectively. Conclusions The ATII LCL metagenome hosts putative peptidases and biosynthetic genes that confer antibiotic and anti-cancer effects. The tested clones exhibited promising antibacterial activities against safe relative strains to ESKAPE pathogens and Mycobacterium tuberculosis. Thus, searching the microbial dark matter of extreme environments is a promising approach to identify new molecules with pharmaceutical potential use.https://doi.org/10.1186/s12934-022-01835-zMetagenomicsNatural productsCancerAntibioticsRed SeaSpecialized metabolites |
| spellingShingle | Laila Ziko Omnia AbdelRaheem Marina Nabil Ramy K. Aziz Rania Siam Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity Microbial Cell Factories Metagenomics Natural products Cancer Antibiotics Red Sea Specialized metabolites |
| title | Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity |
| title_full | Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity |
| title_fullStr | Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity |
| title_full_unstemmed | Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity |
| title_short | Bioprospecting the microbiome of Red Sea Atlantis II brine pool for peptidases and biosynthetic genes with promising antibacterial activity |
| title_sort | bioprospecting the microbiome of red sea atlantis ii brine pool for peptidases and biosynthetic genes with promising antibacterial activity |
| topic | Metagenomics Natural products Cancer Antibiotics Red Sea Specialized metabolites |
| url | https://doi.org/10.1186/s12934-022-01835-z |
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