An ultrasensitive microfluidic approach reveals correlations between the physico-chemical and biological activity of experimental peptide antibiotics.
Authors
Cama, Jehangir
Fletcher, Marcus
Hammond, Katharine
Ryadnov, Maxim G
Keyser, Ulrich F
Pagliara, Stefano
Publication Date
2022-03-07Journal Title
Sci Rep
ISSN
2045-2322
Publisher
Springer Science and Business Media LLC
Volume
12
Issue
1
Language
en
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Cama, J., Al Nahas, K., Fletcher, M., Hammond, K., Ryadnov, M. G., Keyser, U. F., & Pagliara, S. (2022). An ultrasensitive microfluidic approach reveals correlations between the physico-chemical and biological activity of experimental peptide antibiotics.. Sci Rep, 12 (1) https://doi.org/10.1038/s41598-022-07973-z
Description
Funder: Winton Programme for the Physics of Sustainability
Funder: Cambridge-NPL studentship
Funder: Trinity-Henry Barlow Scholarship
Funder: Department for Business, Energy and Industrial Strategy, UK Government; doi: http://dx.doi.org/10.13039/100011693
Abstract
Antimicrobial resistance challenges the ability of modern medicine to contain infections. Given the dire need for new antimicrobials, polypeptide antibiotics hold particular promise. These agents hit multiple targets in bacteria starting with their most exposed regions-their membranes. However, suitable approaches to quantify the efficacy of polypeptide antibiotics at the membrane and cellular level have been lacking. Here, we employ two complementary microfluidic platforms to probe the structure-activity relationships of two experimental series of polypeptide antibiotics. We reveal strong correlations between each peptide's physicochemical activity at the membrane level and biological activity at the cellular level. We achieve this knowledge by assaying the membranolytic activities of the compounds on hundreds of individual giant lipid vesicles, and by quantifying phenotypic responses within clonal bacterial populations with single-cell resolution. Our strategy proved capable of detecting differential responses for peptides with single amino acid substitutions between them, and can accelerate the rational design and development of peptide antimicrobials.
Keywords
Article, /631/45, /631/1647, /631/57, /631/154, /631/326, article
Sponsorship
European Research Council (647144)
EPSRC (2148169)
Identifiers
s41598-022-07973-z, 7973
External DOI: https://doi.org/10.1038/s41598-022-07973-z
This record's URL: https://www.repository.cam.ac.uk/handle/1810/334732
Rights
Licence:
http://creativecommons.org/licenses/by/4.0/
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