Gram-Positive Bacterial Membrane-Based Biosensor for Multimodal Investigation of Membrane–Antibiotic Interactions
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Published:2024-01-15
Issue:1
Volume:14
Page:45
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ISSN:2079-6374
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Container-title:Biosensors
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language:en
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Short-container-title:Biosensors
Author:
Bint-E-Naser Samavi Farnush1ORCID, Mohamed Zeinab Jushkun2, Chao Zhongmou1, Bali Karan3, Owens Róisín M.3ORCID, Daniel Susan1ORCID
Affiliation:
1. Robert F. Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA 2. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA 3. Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge CB3 0AS, UK
Abstract
As membrane-mediated antibiotic resistance continues to evolve in Gram-positive bacteria, the development of new approaches to elucidate the membrane properties involved in antibiotic resistance has become critical. Membrane vesicles (MVs) secreted by the cytoplasmic membrane of Gram-positive bacteria contain native components, preserving lipid and protein diversity, nucleic acids, and sometimes virulence factors. Thus, MV-derived membrane platforms present a great model for Gram-positive bacterial membranes. In this work, we report the development of a planar bacterial cytoplasmic membrane-based biosensor using MVs isolated from the Bacillus subtilis WT strain that can be coated on multiple surface types such as glass, quartz crystals, and polymeric electrodes, fostering the multimodal assessment of drug–membrane interactions. Retention of native membrane components such as lipoteichoic acids, lipids, and proteins is verified. This biosensor replicates known interaction patterns of the antimicrobial compound, daptomycin, with the Gram-positive bacterial membrane, establishing the applicability of this platform for carrying out biophysical characterization of the interactions of membrane-acting antibiotic compounds with the bacterial cytoplasmic membrane. We report changes in membrane viscoelasticity and permeability that correspond to partial membrane disruption when calcium ions are present with daptomycin but not when these ions are absent. This biomembrane-based biosensing platform enables an assessment of membrane biophysical characteristics during exposure to antibiotic drug candidates to aid in identifying compounds that target membrane disruption as a mechanism of action.
Funder
Defense Advanced Research Projects Agency (DARPA) Army Research Office National Institutes of Health through Venatorx Pharmaceuticals National Science Foundation Engineering and Physical Sciences Research Council (EPSRC)-DTP PhD studentship Cornell University Materials Research Science and Engineering Center
Subject
Clinical Biochemistry,General Medicine,Analytical Chemistry,Biotechnology,Instrumentation,Biomedical Engineering,Engineering (miscellaneous)
Reference90 articles.
1. Willdigg, J.R., and Helmann, J.D. (2021). Mini Review: Bacterial Membrane Composition and Its Modulation in Response to Stress. Front. Mol. Biosci., 8. 2. Silhavy, T.J., Kahne, D., and Walker, S. (2010). The Bacterial Cell Envelope. Cold Spring Harb. Perspect. Biol., 2. 3. Bacterial Lipid Composition and the Antimicrobial Efficacy of Cationic Steroid Compounds (Ceragenins);Epand;Biochim. Biophys. Acta Biomembr.,2007 4. The Alanine Ester Substitution of Lipoteichoic Acid (LTA) in Staphylococcus Aureus;Fischer;FEBS Lett.,1980 5. Kamar, R., Réjasse, A., Jéhanno, I., Attieh, Z., Courtin, P., Chapot-Chartier, M.-P., Nielsen-Leroux, C., Lereclus, D., el Chamy, L., and Kallassy, M. (2017). DltX of Bacillus Thuringiensis Is Essential for D-Alanylation of Teichoic Acids and Resistance to Antimicrobial Response in Insects. Front. Microbiol., 8.
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