Targeted delivery of narrow-spectrum protein antibiotics to the lower gastrointestinal tract in a murine model of escherichia coli colonization

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Carpena, Nuria and Richards, Kerry and Gonzalez, Teresita D. J. Bello and Bravo-Blas, Alberto and Housden, Nicholas G. and Gerasimidis, Konstantinos and Milling, Simon W. F. and Douce, Gillian and Malik, Danish J. and Walker, Daniel (2021) Targeted delivery of narrow-spectrum protein antibiotics to the lower gastrointestinal tract in a murine model of escherichia coli colonization. Frontiers in Microbiology, 12. pp. 1-12. 670535. ISSN 1664-302X (https://doi.org/10.3389/fmicb.2021.670535)

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Abstract

Bacteriocins are narrow-spectrum protein antibiotics that could potentially be used to engineer the human gut microbiota. However, technologies for targeted delivery of proteins to the lower gastrointestinal (GI) tract in preclinical animal models are currently lacking. In this work, we have developed methods for the microencapsulation of Escherichia coli targeting bacteriocins, colicin E9 and Ia, in a pH responsive formulation to allow their targeted delivery and controlled release in an in vivo murine model of E. coli colonization. Membrane emulsification was used to produce a water-in-oil emulsion with the water-soluble polymer subsequently cross-linked to produce hydrogel microcapsules. The microcapsule fabrication process allowed control of the size of the drug delivery system and a near 100% yield of the encapsulated therapeutic cargo. pH-triggered release of the encapsulated colicins was achieved using a widely available pH-responsive anionic copolymer in combination with alginate biopolymers. In vivo experiments using a murine E. coli intestinal colonization model demonstrated that oral delivery of the encapsulated colicins resulted in a significant decrease in intestinal colonization and reduction in E. coli shedding in the feces of the animals. Employing controlled release drug delivery systems such as that described here is essential to enable delivery of new protein therapeutics or other biological interventions for testing within small animal models of infection. Such approaches may have considerable value for the future development of strategies to engineer the human gut microbiota, which is central to health and disease.

ORCID iDs

Carpena, Nuria, Richards, Kerry, Gonzalez, Teresita D. J. Bello, Bravo-Blas, Alberto, Housden, Nicholas G., Gerasimidis, Konstantinos, Milling, Simon W. F., Douce, Gillian, Malik, Danish J. and Walker, Daniel ORCID logoORCID: https://orcid.org/0000-0002-4206-2942;
  • Item type:Article
    ID code:86204
    Dates:
    Date
    Event
    14 October 2021
    Published
    21 September 2021
    Accepted
    21 February 2021
    Submitted
    Notes:Carpena N, Richards K, Bello Gonzalez TDJ, Bravo-Blas A, Housden NG, Gerasimidis K, Milling SWF, Douce G, Malik DJ and Walker D (2021) Targeted Delivery of Narrow-Spectrum Protein Antibiotics to the Lower Gastrointestinal Tract in a Murine Model of Escherichia coli Colonization. Front. Microbiol. 12:670535 doi: 10.3389/fmicb.2021.670535 Copyright © 2021 Carpena, Richards, Bello Gonzalez, Bravo-Blas, Housden, Gerasimidis, Milling, Douce, Malik and Walker. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
    Subjects:Science > Microbiology
    Medicine > Public aspects of medicine
    Medicine > Pharmacy and materia medica
    Department:Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
    Depositing user: Pure Administrator
    Date deposited:20 Jul 2023 12:55
    Last modified:11 Nov 2024 14:00
    URI:https://strathprints.strath.ac.uk/id/eprint/86204
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