Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved]
Background: Fc-mannose-binding lectin (FcMBL), an engineered version of the blood opsonin MBL that contains the carbohydrate recognition domain (CRD) and flexible neck regions of MBL fused to the Fc portion of human IgG1, has been shown to bind various microbes and pathogen-associated molecular patt...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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F1000 Research Ltd
2019-01-01
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| Series: | F1000Research |
| Online Access: | https://f1000research.com/articles/8-108/v1 |
| _version_ | 1818960420437753856 |
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| author | Benjamin T. Seiler Mark Cartwright Alexandre L. M. Dinis Shannon Duffy Patrick Lombardo David Cartwright Elana H. Super Jacqueline Lanzaro Kristen Dugas Michael Super Donald E. Ingber |
| author_facet | Benjamin T. Seiler Mark Cartwright Alexandre L. M. Dinis Shannon Duffy Patrick Lombardo David Cartwright Elana H. Super Jacqueline Lanzaro Kristen Dugas Michael Super Donald E. Ingber |
| author_sort | Benjamin T. Seiler |
| collection | DOAJ |
| description | Background: Fc-mannose-binding lectin (FcMBL), an engineered version of the blood opsonin MBL that contains the carbohydrate recognition domain (CRD) and flexible neck regions of MBL fused to the Fc portion of human IgG1, has been shown to bind various microbes and pathogen-associated molecular patterns (PAMPs). FcMBL has also been used to create an enzyme-linked lectin sorbent assay (ELLecSA) for use as a rapid (<1 h) diagnostic of bloodstream infections. Methods: Here we extended this work by using the ELLecSA to test FcMBL’s ability to bind to more than 190 different isolates from over 95 different pathogen species. Results: FcMBL bound to 85% of the isolates and 97 of the 112 (87%) different pathogen species tested, including bacteria, fungi, viral antigens and parasites. FcMBL also bound to PAMPs including, lipopolysaccharide endotoxin (LPS) and lipoteichoic acid (LTA) from Gram-negative and Gram-positive bacteria, as well as lipoarabinomannan (LAM) and phosphatidylinositol mannoside 6 (PIM6) from Mycobacterium tuberculosis. Conclusions: The efficiency of pathogen detection and variation between binding of different strains of the same species could be improved by treating the bacteria with antibiotics, or mechanical disruption using a bead mill, prior to FcMBL capture to reveal previously concealed binding sites within the bacterial cell wall. As FcMBL can bind to pathogens and PAMPs in urine as well as blood, its broad-binding capability could be leveraged to develop a variety of clinically relevant technologies, including infectious disease diagnostics, therapeutics, and vaccines. |
| first_indexed | 2024-12-20T11:57:15Z |
| format | Article |
| id | doaj.art-5ff158b5826946c09dbb5b9037aaf014 |
| institution | Directory Open Access Journal |
| issn | 2046-1402 |
| language | English |
| last_indexed | 2024-12-20T11:57:15Z |
| publishDate | 2019-01-01 |
| publisher | F1000 Research Ltd |
| record_format | Article |
| series | F1000Research |
| spelling | doaj.art-5ff158b5826946c09dbb5b9037aaf0142022-12-21T19:41:37ZengF1000 Research LtdF1000Research2046-14022019-01-01810.12688/f1000research.17447.119079Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved]Benjamin T. Seiler0Mark Cartwright1Alexandre L. M. Dinis2Shannon Duffy3Patrick Lombardo4David Cartwright5Elana H. Super6Jacqueline Lanzaro7Kristen Dugas8Michael Super9Donald E. Ingber10Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAWyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, 02115, USAVascular Biology Program, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts, 02115, USABackground: Fc-mannose-binding lectin (FcMBL), an engineered version of the blood opsonin MBL that contains the carbohydrate recognition domain (CRD) and flexible neck regions of MBL fused to the Fc portion of human IgG1, has been shown to bind various microbes and pathogen-associated molecular patterns (PAMPs). FcMBL has also been used to create an enzyme-linked lectin sorbent assay (ELLecSA) for use as a rapid (<1 h) diagnostic of bloodstream infections. Methods: Here we extended this work by using the ELLecSA to test FcMBL’s ability to bind to more than 190 different isolates from over 95 different pathogen species. Results: FcMBL bound to 85% of the isolates and 97 of the 112 (87%) different pathogen species tested, including bacteria, fungi, viral antigens and parasites. FcMBL also bound to PAMPs including, lipopolysaccharide endotoxin (LPS) and lipoteichoic acid (LTA) from Gram-negative and Gram-positive bacteria, as well as lipoarabinomannan (LAM) and phosphatidylinositol mannoside 6 (PIM6) from Mycobacterium tuberculosis. Conclusions: The efficiency of pathogen detection and variation between binding of different strains of the same species could be improved by treating the bacteria with antibiotics, or mechanical disruption using a bead mill, prior to FcMBL capture to reveal previously concealed binding sites within the bacterial cell wall. As FcMBL can bind to pathogens and PAMPs in urine as well as blood, its broad-binding capability could be leveraged to develop a variety of clinically relevant technologies, including infectious disease diagnostics, therapeutics, and vaccines.https://f1000research.com/articles/8-108/v1 |
| spellingShingle | Benjamin T. Seiler Mark Cartwright Alexandre L. M. Dinis Shannon Duffy Patrick Lombardo David Cartwright Elana H. Super Jacqueline Lanzaro Kristen Dugas Michael Super Donald E. Ingber Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved] F1000Research |
| title | Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved] |
| title_full | Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved] |
| title_fullStr | Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved] |
| title_full_unstemmed | Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved] |
| title_short | Broad-spectrum capture of clinical pathogens using engineered Fc-mannose-binding lectin enhanced by antibiotic treatment [version 1; peer review: 2 approved] |
| title_sort | broad spectrum capture of clinical pathogens using engineered fc mannose binding lectin enhanced by antibiotic treatment version 1 peer review 2 approved |
| url | https://f1000research.com/articles/8-108/v1 |
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