Synthetic phage-inducible chromosomal islands (PICIs) for diagnostic and therapeutic applications

Ibarra Chavez, Victor Rodrigo (2019) Synthetic phage-inducible chromosomal islands (PICIs) for diagnostic and therapeutic applications. PhD thesis, University of Glasgow.

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With the emerging global threat of antimicrobial resistance, diagnosis and treatment of infectious diseases has become more difficult than ever. We need to consider new paradigms in therapy and innovative alternatives that can allow us to rapidly detect bacteria at the point-of-care and efficiently eliminate pathogens without promoting the dissemination of virulent factors. This thesis aims to develop a new alternative for the development of new applications for therapy and diagnostics of bacteria. Here we use synthetic phage-inducible chromosomal islands (PICIs) to combine the two concepts of diagnostics and therapy to "seek & destroy" specific bacteria. These novel biosensors open a series of applications for the detection and elimination of the pathogen by using the pathogen itself to modify its genome specifically to produce a reporter (seek) and/or a killing switch (destroy).

Here we demonstrate that PICIs can achieve high transfer and sensitivity compared to phages, while improving a methodology to study the effects on the viability and detection of pathogens. We engineered PICIs to carry a series of synthetic gene circuits in order to enable the detection of cells and potential sorting of pathogens, while avoiding the spread of antimicrobial genes onto the target cell. Further modifications prove that PICIs can be used as a Trojan-horse to deliver lethal payloads into target cells. Here, we exploited the PICI components by which they highjack the phage machinery to promote their spread.
Taken together, this reinforces the recent interests for developing alternative ways to diagnose and treat bacterial infections. This thesis opens a range of applications in using other types of PICIs recently characterised as Synthetic Biology tools for portable diagnostics and prophylactic methods.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: This project was funded by the Mexican National Council of Science and Technology (CONACyT) and collaboration with Prof. José R. Penadés.
Keywords: Phage-inducible chromosomal islands, bacteriophage, point-of-care diagnostics, CRISPR-Cas, phage therapy.
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QR Microbiology
Colleges/Schools: College of Science and Engineering > School of Engineering > Biomedical Engineering
Supervisor's Name: Cooper, Prof. Jonathan M. and Reboud, Dr. Julien
Date of Award: 2019
Embargo Date: 7 February 2022
Depositing User: Mr Victor Rodrigo Ibarra Chavez
Unique ID: glathesis:2019-41003
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 07 Feb 2019 13:22
Last Modified: 05 Mar 2020 22:07
Thesis DOI: 10.5525/gla.thesis.41003

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