Mycobacteriales: a Raman characterisation study and an investigation into diagnostic avenues for bovine and human tuberculosis

Macgregor-Fairlie, Michael ORCID: 0000-0003-4600-0893 (2024). Mycobacteriales: a Raman characterisation study and an investigation into diagnostic avenues for bovine and human tuberculosis. University of Birmingham. Ph.D.

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Abstract

Despite the overshadowing threat of the COVID-19 pandemic, tuberculosis (TB) persists as a major global health challenge, responsible for an estimated 1.6 million deaths in 2021 and afflicting approximately one-third of the global population. The World Health Organization's urgent appeal for cost-effective, accessible, sensitive, and specific diagnostic tools underscores the pressing need for innovative solutions.
This thesis was initiated by exploring the diagnostic potential of two promising technological avenues: the gene-editing tool CRISPR-Cas12a and Raman spectroscopy. At the inception of the project, these technologies remained largely uncharacterised within the context of TB diagnosis.
The investigation conducted throughout this research subsequently revealed a significant gap in the current knowledge base pertaining to the application of Raman spectroscopy in TB diagnostics. Specifically, no prior research had considered the influence of the microbiome on the Raman spectra of test results.
This thesis delves deeper into this uncharted territory, focusing on the Raman characterisation of Mycobacterium tuberculosis and Mycobacterium bovis BCG. Using In silico methods and examining the bacteria's cell wall lipids, the research illuminates the physical components contributing to the Raman spectra of these bacteria, unearthing new spectral elements in the process. Furthermore, deploying a collaboratively-developed Python package for multivariate statistical analysis, this study differentiates subtle variations between M. bovis BCG and other closely related bacteria using the bovine microbiome as an experimental model, an aspect not previously considered.
This research enhances our understanding of the Raman spectra of organisms similar to M. bovis BCG and, for the first time, takes into account the role of the microbiome. In the process, it broadens our knowledge of these complex organisms. By employing open-source statistical tools, the thesis also contributes to wider applications within the field.
Ultimately, this research hopes to facilitate the application of these diagnostic tools beyond tuberculosis, offering a potent weapon in humanity's ongoing battle against infectious diseases.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):