Biomimetic Electronic Devices for Measuring Bacterial Membrane Disruption.
Artim, Christine M
Faria, Gregorio C
Duong, Duc D
Alabi, Christopher A
Advanced materials (Deerfield Beach, Fla.)
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Pitsalidis, C., Pappa, A., Porel, M., Artim, C. M., Faria, G. C., Duong, D. D., Alabi, C. A., et al. (2018). Biomimetic Electronic Devices for Measuring Bacterial Membrane Disruption.. Advanced materials (Deerfield Beach, Fla.), 30 (39), e1803130. https://doi.org/10.1002/adma.201803130
The block in the antibiotic discovery pipeline is reaching crisis levels, exacerbated by poor antibiotic stewardship. Antibiotic discovery has slowed severely, in part due to failures of target-focused screening platforms in identifying compounds which disrupt bacterial membranes, a neglected, yet obvious target due to substantial differences from mammalian membranes.[4,5] In vitro screening methods using lipids can elucidate interactions with the membrane at the molecular level, greatly aiding the design and rapid development of new compounds.[6,7] One outstanding unresolved issue is the availability of a scalable and reliable technology to interface with robust model membranes, particularly bacterial ones. Unperturbed lipid layers are highly insulating electrically. This property is extremely sensitive to interactions with membrane disrupting species [8,9] and may be characterized by coupling with an electronic transducer, in this case the Organic Electrochemical Transistor (OECT). Here we show that lipid monolayers assembled at a liquid-liquid interface are a suitable model for characterizing compounds that disrupt the cell membrane. These monolayers block ion flow when placed between the gating electrode and the transistor channel, resulting in a substantial decrease of the gate-induced current modulation in the channel. The antibacterial compound Polymyxin B (PMB) was added to such a blocking ‘bacterial-like’ lipid monolayer, resulting in recovery of the modulation, increasing conductance. Further illustrating the potential of this device in characterizing novel anti-bacterial compounds, we show that molecular scale differences in the recently described antibacterial amine-based oligothioetheramides (AOTs) can be discerned. Indeed, the amplitude of the device response correlates well with the relative performance of the compounds in a traditional bacterial killing assay using whole cells. We anticipate that the ability to carry out a real-time, sensitive and quantitative assessment of the activity of novel membrane-disrupting compounds can revolutionize the rapid characterization of antibacterial compounds, especially when combined with the potential of organic electronics for being massively scalable using semiconductor microfabrication technology.
Cell Membrane, Polymyxin B, Phospholipids, Biomimetics
Marie Curie ITN OrgBIO Project No. 607896 Agence Nationale de la Recherche 3Bs project Stanford-France Center National Science Foundation (Award #DMR 1507826) Burroughs Wellcome Fund Collaborative Research Travel Grant (#1016253)
External DOI: https://doi.org/10.1002/adma.201803130
This record's URL: https://www.repository.cam.ac.uk/handle/1810/280307