Evolutionary Genomics of Cystic Fibrosis and Nosocomial Pathogens of the Mycobacterium abscessus species complex
type: CreativeWork
description: The $\textit{Mycobacterium abscessus}$ species complex (MABSC) consists of three subspecies, $\textit{M. a. abscessus}$, $\textit{M. a. massiliense}$ and $\textit{M. a. bolletii}$. All three of these subspecies are capable of causing opportunistic pulmonary and skin and soft tissue infections in immunocompromised individuals. Infections caused by the MABSC are particularly serious in people with underlying lung conditions such as Cystic Fibrosis (CF) as these organisms are highly antibiotic resistant and the currently available treatment is toxic. This has resulted in treatment of MABSC infections failing in up to 50% of cases. Given the increasing prevalence globally of infections caused by the MABSC, particularly in individuals with CF, there is increased urgency to improve the treatment available for MABSC infections. The overall aim of this project was to use genomic analyses to increase our understanding of how the MABSC has evolved to become an opportunistic pathogen, which in turn could potentially uncover promising targets for the development of novel antibiotics. Genomic analysis of the MABSC has already shown that lineages of the MABSC are capable of indirect person to person transmission and the extent to which transmission contributed to the increasing prevalence of MABSC in people with CF became evident when the MABSC global population structure was determined. This showed that 70% of the MABSC isolates from people with CF were attributed to lineages made up of densely clustered isolates, where acquisition via indirect person-to-person transmission, as opposed to from the environment, was more likely. This thesis used population genomic approaches to i) investigate the genetic factors that drove the emergence of the most prevalent MABSC lineages, ii) look for evidence of convergence after the clonal expansion of these lineages to understand how the MABSC was continuing to adapt and spread amongst people with CF and iii) to examine the within host evolut…
abstract: The $\textit{Mycobacterium abscessus}$ species complex (MABSC) consists of three subspecies, $\textit{M. a. abscessus}$, $\textit{M. a. massiliense}$ and $\textit{M. a. bolletii}$. All three of these subspecies are capable of causing opportunistic pulmonary and skin and soft tissue infections in immunocompromised individuals. Infections caused by the MABSC are particularly serious in people with underlying lung conditions such as Cystic Fibrosis (CF) as these organisms are highly antibiotic resistant and the currently available treatment is toxic. This has resulted in treatment of MABSC infections failing in up to 50% of cases. Given the increasing prevalence globally of infections caused by the MABSC, particularly in individuals with CF, there is increased urgency to improve the treatment available for MABSC infections. The overall aim of this project was to use genomic analyses to increase our understanding of how the MABSC has evolved to become an opportunistic pathogen, which in turn could potentially uncover promising targets for the development of novel antibiotics. Genomic analysis of the MABSC has already shown that lineages of the MABSC are capable of indirect person to person transmission and the extent to which transmission contributed to the increasing prevalence of MABSC in people with CF became evident when the MABSC global population structure was determined. This showed that 70% of the MABSC isolates from people with CF were attributed to lineages made up of densely clustered isolates, where acquisition via indirect person-to-person transmission, as opposed to from the environment, was more likely. This thesis used population genomic approaches to i) investigate the genetic factors that drove the emergence of the most prevalent MABSC lineages, ii) look for evidence of convergence after the clonal expansion of these lineages to understand how the MABSC was continuing to adapt and spread amongst people with CF and iii) to examine the within host evolut…
author: Everall, Isobel
language: en
keywords: Bioinformatics, Bacterial genomics, Mycobacteria, Cystic Fibrosis, Nontuberculous Mycobacteria
license: https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/69021047-1e86-4f37-995e-7e8c90e81cc2/download
license: https://www.rioxx.net/licenses/all-rights-reserved/
date published: 2019-04-27
date modified: 2026-07-22T22:24:04Z
provider: Cambridge University
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Cambridge

PropertyValue
property ID: DOI
value: 10.17863/CAM.37771