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The interrelationship of strain diversity, virulence and patient ethnicity for tuberculosis in the Midlands, UK

Smith, Helen Elizabeth (2013)
Ph.D. thesis, University of Birmingham.

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Abstract

This study examined the relationship between Mycobacterium tuberculosis global clades and patient origin. In the UK, the rate of tuberculosis is higher amongst patients who originated from the Indian subcontinent (ISC), where two dominant lineages are present, the Central Asian Strain (CAS) and the East African Indian (EAI) lineage. Mycobacterial interspersed units containing variable number of tandem repeats DNA fingerprinting of M. tuberculosis strains isolated from UK patients who originated from the ISC, as defined by novel software, identified that CAS was the most prevalent clade (39%) and EAI was the third most prevalent clade (15%). To further elucidate the relationship between host origin and strain lineage, two rigorous new models of infection were developed which assessed mycobacterial growth and host cell response. The monocyte-derived macrophage model was more appropriate for measuring cytototoxicity than the THP-1 cell model as in the absence of infection, 50% of THP-1 cells died compared to 2% of macrophages. CAS strains caused 1.5 fold more cell necrosis and their growth was four fold higher than EAI strains in the monocyte-derived macrophage model. Finally, the response of polarised monocyte-derived macrophages from Asian and Caucasian donors to different M. tuberculosis lineages was compared. CAS strains grew preferentially better in M2 macrophages from Asian donors. The prevalence of CAS in the Midlands is likely to be due to a combination of specific strain importation and increased ability of this strain to transmit to the population present in the Midlands.

Type of Work:Ph.D. thesis.
Supervisor(s):Hawkey, Peter and Lammas, Tony
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Immunity and Infection
Subjects:QR Microbiology
QR180 Immunology
RC Internal medicine
Institution:University of Birmingham
ID Code:4452
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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