Evolutionary Genomics of Cystic Fibrosis and Nosocomial Pathogens of the Mycobacterium abscessus species complex
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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 evolution of these pathogens to uncover how these environmental organisms were adapting to the CF lung. This thesis also used whole genome sequencing to explore the largest known outbreak of MABSC infections, a post-surgical wound infection epidemic in Brazil.
Through this research the emergence of the most prevalent MABSC lineages were found to
be driven by increased opportunity, probably due to the increased number of people with CF
surviving longer, as opposed to the acquisition of a common genetic determinant. Not
enough signal was detected after the clonal expansion of the most prevalent MABSC
lineages to come to strong conclusions about genetic factors driving their continuing
expansion, but strong evidence of convergent evolution was detected between MABSC
isolates evolving over time within the host. The MABSC was shown to be potentially using a
similar central regulatory network in response to environmental cues from the phagosome to
that of
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Floto, Rodrigo Andres