Multiparametric Sensing of Outer Membrane Vesicle-Derived Supported Lipid Bilayers Demonstrates the Specificity of Bacteriophage Interactions

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Bali, Karan; paragon-plus: 6038193 
McCoy, Reece; paragon-plus: 6446028 
Lu, Zixuan; paragon-plus: 5871222; orcid: 0000-0002-3689-4283 
Treiber, Jeremy; paragon-plus: 6467721 
Savva, Achilleas; orcid: 0000-0002-0197-0290; paragon-plus: 3794574 

The use of bacteriophages, viruses that specifically infect bacteria, as antibiotics has become an area of great interest in recent years as the effectiveness of conventional antibiotics recedes. The detection of phage interactions with specific bacteria in a rapid and quantitative way is key for identifying phages of interest for novel antimicrobials. Outer membrane vesicles (OMVs) derived from Gram-negative bacteria can be used to make supported lipid bilayers (SLBs) and therefore in vitro membrane models that contain naturally occurring components of the bacterial outer membrane. In this study, we employed Escherichia coli OMV derived SLBs and use both fluorescent imaging and mechanical sensing techniques to show their interactions with T4 phage. We also integrate these bilayers with microelectrode arrays (MEAs) functionalized with the conducting polymer PEDOT:PSS and show that the pore forming interactions of the phages with the SLBs can be monitored using electrical impedance spectroscopy. To highlight our ability to detect specific phage interactions, we also generate SLBs using OMVs derived from Citrobacter rodentium, which is resistant to T4 phage infection, and identify their lack of interaction with the phage. The work presented here shows how interactions occurring between the phages and these complex SLB systems can be monitored using a range of experimental techniques. We believe this approach can be used to identify phages that work against bacterial strains of interest, as well as more generally to monitor any pore forming structure (such as defensins) interacting with bacterial outer membranes, and thus aid in the development of next generation antimicrobials.

QCM-D, supported lipid bilayer, fluorescent microscopy, PEDOT:PSS, bacteriophage-membrane interactions, outer membrane vesicles
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ACS Biomaterials Science & Engineering
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American Chemical Society
Defense Advanced Research Projects Agency (W911NF-18-2-0152)
Wellcome (089703/Z/09/Z)
Wellcome (3-3249/Z/16/Z)
H2020 Marie Sklodowska-Curie Actions (895801)
Medical Research Council (MR/K015850/1)
Medical Research Council (MR/K02292X/1)
Engineering and Physical Sciences Research Council (EP/H018301/1)
Engineering and Physical Sciences Research Council (EP/L015889/1)
Engineering and Physical Sciences Research Council (EP/S022953/1)
Royal Society (URF/R1/221795)
Infinitus (NA)
MedImmune (NA)