Pathogen-specific antimicrobials engineered de novo through membrane-protein biomimicry
Autor: | Christy George, John N. Alumasa, Adam Bolotsky, Michael D. Howe, Anthony D. Baughn, Dennis C. Chan, Andrew W. Simonson, Scott H. Medina, Elizabeth A. Proctor, Tapas K. Mal, Kenneth C. Keiler, Agustey S. Mongia, Atip Lawanprasert, Matthew R. Aronson, Aida Ebrahimi |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
medicine.drug_class Antimicrobial peptides Antibiotics Biomedical Engineering Medicine (miscellaneous) Bioengineering Biology Article Microbiology Mycobacterium tuberculosis 03 medical and health sciences 0302 clinical medicine Bacterial Proteins medicine Humans Peptide sequence Pathogen Lung Molecular Mimicry Membrane Proteins biology.organism_classification Transmembrane protein Computer Science Applications Anti-Bacterial Agents 030104 developmental biology Bacterial Outer Membrane Membrane protein Bacterial outer membrane Peptides 030217 neurology & neurosurgery Biotechnology |
Zdroj: | Nature biomedical engineering |
ISSN: | 2157-846X |
Popis: | Precision antimicrobials aim to kill pathogens without damaging commensal bacteria in the host, and thereby cure disease without antibiotic-associated dysbiosis. Here we report the de novo design of a synthetic host defence peptide that targets a specific pathogen by mimicking key molecular features of the pathogen's channel-forming membrane proteins. By exploiting physical and structural vulnerabilities within the pathogen's cellular envelope, we designed a peptide sequence that undergoes instructed tryptophan-zippered assembly within the mycolic acid-rich outer membrane of Mycobacterium tuberculosis to specifically kill the pathogen without collateral toxicity towards lung commensal bacteria or host tissue. These mycomembrane-templated assemblies elicit rapid mycobactericidal activity and enhance the potency of antibiotics by improving their otherwise poor diffusion across the rigid M. tuberculosis envelope with respect to agents that exploit transmembrane protein channels for antimycobacterial activity. This biomimetic strategy may aid the design of other narrow-spectrum antimicrobial peptides. |
Databáze: | OpenAIRE |
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