Using phages to Treat Urinary Tract Infections: Predicting phage susceptibility using bacterial genome and MALDI-TOF data

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2023-09-07

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Saudi Digital Library

Abstract

AMR, and MDR present substantial challenges for individuals and have also become a global concern. This has resulted in these infections, gaining increasing attention. Bacteriophages have become the go-to in dealing with bacteria resistance and decreasing the number of mortalities. For this project, instruments like the bacteria genome sequence and MALDI-TOF data will be used to gain predictions of phage susceptibility and serotypes. A group of 16 phages was collected in the lab with at least one manufactured host. This project obtained 70 clinical strains from the Bristol University Hospital. Two techniques were employed in this project: spot test and plague essay. Both methods seek to measure the concentration of the bacteriophage and evaluate the virus’ effectiveness. The serotypes included in this study are ST131, ST69, ST73, and ST95. The project concluded, the gene pattern of ST131 responds weakly to most phages and all concentrations. ST73_35 was the most sensitive in 108=114, 106=87 104=51. Some strains were more sensitive than the others ST73 and ST95 this is may allow to make predictions in terms of family species or sequencing. On the other hand, ST131 was the most resistance strain and then ST69, this would make more challenging to work for phage predictor. It can be noted that JK08 performing the best with strains. On the other hand, the worst phage UP15 1×104 shows more resistance to strain. In the event that further studies with Whole Genome Sequencing and MALDI-TOF were conducted to confirm this mechanism, so that would be able to predict some genes responsible for susceptibility or resistance. The outcome of this project will demonstrate a platform of a broad collection of E. coli strains that might finds the correlation of sequence types with MALDI-TOF and WGS data so we can make predictions on host range.

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Determine if there is a relationship between E. coli bacterial genomes and bacteriophage susceptibility. Currently there no methods to predict if phages will be successful. This information would allow doctors to use phages efficiently within a clinical setting. It is quite possible that there is a relationship between susceptibility and the information in the bacterial genome and this could be integrated into standard care. It is also possible that susceptibility information can be captured from MALDI (mass-spec) data from strains, as is currently commonly carried out in hospitals. This project will address the problem of predicting phage susceptibility by screening our phage collections on a large set of clinical strains of E. coli to see if we can correlate information from genomes and MALDI spectra with phage susceptibility. You will work with me, alongside a team of phage researchers in my lab and clinical team from Bristol to help interpret the bacterial data and this project will help provide fundamental data needed lay the foundation to integrate phages into mainstream medicine in the UK.

Keywords

Susceptible, Bacteriophages, UTIs, Predicting, Bacteraemia, MALDI-TOF, WGS

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