Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp.
We have isolated and characterized a novel antibacterial peptide, CMB001, following an extensive screening effort of bacterial species isolated from diverse environmental sources. The bacterium that produces CMB001 is characterized as a Gram (+) bacillus sharing approximately 98.9% 16S rRNA sequence...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2020.598789/full |
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| author | Jerzy Karczewski Stephen P. Krasucki Papa Nii Asare-Okai Carl Diehl Andrew Friedman Christine M. Brown Yukari Maezato Stephen J. Streatfield |
| author_facet | Jerzy Karczewski Stephen P. Krasucki Papa Nii Asare-Okai Carl Diehl Andrew Friedman Christine M. Brown Yukari Maezato Stephen J. Streatfield |
| author_sort | Jerzy Karczewski |
| collection | DOAJ |
| description | We have isolated and characterized a novel antibacterial peptide, CMB001, following an extensive screening effort of bacterial species isolated from diverse environmental sources. The bacterium that produces CMB001 is characterized as a Gram (+) bacillus sharing approximately 98.9% 16S rRNA sequence homology with its closest match, Paenibacillus kyungheensis. The molecule has been purified to homogeneity from its cell-free supernatant by a three-step preparative chromatography process. Based on its primary structure, CMB001 shares 81% identity with subtilin and 62% with nisin. CMB001 is active mainly against Gram-positive bacteria and Mycobacteriaceae but it is also active against certain Gram-negative bacteria, including multi-drug resistant Acinetobacter baumannii. It retains full antibacterial activity at neutral pH and displays a low propensity to select for resistance among targeted bacteria. Based on NMR and mass spectrometry, CMB001 forms a unique 3D-structure comprising of a compact backbone with one α-helix and two pseudo-α-helical regions. Screening the structure against the Protein Data Bank (PDB) revealed a partial match with nisin-lipid II (1WCO), but none of the lantibiotics with known structures showed significant structural similarity. Due to its unique structure, resistance profile, relatively broad spectrum and stability under physiological conditions, CMB001 is a promising drug candidate for evaluation in animal models of bacterial infection. |
| first_indexed | 2024-12-22T16:33:10Z |
| format | Article |
| id | doaj.art-5331988770cb4ad98c3b101da797f3b5 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T16:33:10Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5331988770cb4ad98c3b101da797f3b52022-12-21T18:20:01ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2020-11-011110.3389/fmicb.2020.598789598789Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp.Jerzy Karczewski0Stephen P. Krasucki1Papa Nii Asare-Okai2Carl Diehl3Andrew Friedman4Christine M. Brown5Yukari Maezato6Stephen J. Streatfield7Fraunhofer USA Center for Molecular Biotechnology, Newark, DE, United StatesFraunhofer USA Center for Molecular Biotechnology, Newark, DE, United StatesDepartment of Chemistry and Biochemistry, University of Delaware, Newark, DE, United StatesSARomics Biostructures AB, Lund, SwedenFraunhofer USA Center for Molecular Biotechnology, Newark, DE, United StatesFraunhofer USA Center for Molecular Biotechnology, Newark, DE, United StatesFraunhofer USA Center for Molecular Biotechnology, Newark, DE, United StatesFraunhofer USA Center for Molecular Biotechnology, Newark, DE, United StatesWe have isolated and characterized a novel antibacterial peptide, CMB001, following an extensive screening effort of bacterial species isolated from diverse environmental sources. The bacterium that produces CMB001 is characterized as a Gram (+) bacillus sharing approximately 98.9% 16S rRNA sequence homology with its closest match, Paenibacillus kyungheensis. The molecule has been purified to homogeneity from its cell-free supernatant by a three-step preparative chromatography process. Based on its primary structure, CMB001 shares 81% identity with subtilin and 62% with nisin. CMB001 is active mainly against Gram-positive bacteria and Mycobacteriaceae but it is also active against certain Gram-negative bacteria, including multi-drug resistant Acinetobacter baumannii. It retains full antibacterial activity at neutral pH and displays a low propensity to select for resistance among targeted bacteria. Based on NMR and mass spectrometry, CMB001 forms a unique 3D-structure comprising of a compact backbone with one α-helix and two pseudo-α-helical regions. Screening the structure against the Protein Data Bank (PDB) revealed a partial match with nisin-lipid II (1WCO), but none of the lantibiotics with known structures showed significant structural similarity. Due to its unique structure, resistance profile, relatively broad spectrum and stability under physiological conditions, CMB001 is a promising drug candidate for evaluation in animal models of bacterial infection.https://www.frontiersin.org/articles/10.3389/fmicb.2020.598789/fullantimicrobial peptidelantibioticNMRstabilityantibiotic resistanceMRSA |
| spellingShingle | Jerzy Karczewski Stephen P. Krasucki Papa Nii Asare-Okai Carl Diehl Andrew Friedman Christine M. Brown Yukari Maezato Stephen J. Streatfield Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp. Frontiers in Microbiology antimicrobial peptide lantibiotic NMR stability antibiotic resistance MRSA |
| title | Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp. |
| title_full | Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp. |
| title_fullStr | Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp. |
| title_full_unstemmed | Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp. |
| title_short | Isolation, Characterization and Structure Elucidation of a Novel Lantibiotic From Paenibacillus sp. |
| title_sort | isolation characterization and structure elucidation of a novel lantibiotic from paenibacillus sp |
| topic | antimicrobial peptide lantibiotic NMR stability antibiotic resistance MRSA |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2020.598789/full |
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