Towards an understanding of the host’s airway microbiome and the pathogen’s compensatory evolution for drug resistance in human tuberculosis

Ticlla Ccenhua, Monica Roxana. Towards an understanding of the host’s airway microbiome and the pathogen’s compensatory evolution for drug resistance in human tuberculosis. 2021, Doctoral Thesis, University of Basel, Associated Institution, Faculty of Science.


Official URL: https://edoc.unibas.ch/84858/

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Human tuberculosis (TB) is caused by Mycobacterium tuberculosis (MTB), an insidious bacterial pathogen that has silently infected close to a quarter of the human population. Only during the last 20 years, MTB has caused the death of approximately 30 million people; making TB the leading cause of death from a single infectious agent. Despite intensive research to understand which aspects of both the host and pathogen biology make TB so successful across human populations, we are still far from controlling the current global TB epidemic. To complicate things more, drug-resistant MTB has managed to spread and reach epidemic levels in some countries.
In light of the current situation, the World Health Organization (WHO) has called for technological breakthroughs in TB research with priorities set for rapid diagnostics and new preventive and therapeutic treatments. To meet these needs, research is needed in unexplored aspects of the host and pathogen biology that have the potential to fill the current gaps in our understanding of TB. On the host side, the unknown role in TB of commensal microbial communities in the respiratory tract (airway microbiome) is one of such unexplored aspects. And on the pathogen side, the mechanisms behind successful transmissible drug-resistant MTB is another aspect that needs more attention. The work in this thesis is focused on gaining knowledge about both the involvement of the host microbiome in TB and the potential molecular adaptations that evolved in transmissible drug-resistant MTB.
We performed a comparative study of the airway microbiome in a large cohort of TB cases and household contacts. Our findings suggest an interplay among particular members of the airway microbiome, body mass index (BMI), and pulmonary TB pathology. An insight that adds a new dimension to the long-known association between low BMI and pulmonary TB. Finally, to identify adaptations involved in the transmission of drug-resistant MTB, we examined the genomes of drug-resistant MTB from a private nationwide collection of multi-drug resistant MTB isolates. To confirm findings at a global scale, we also included a collection of MTB genomes publicly available as of August 2019. We present evidence of adaptations in the context of rifampicin resistance; particularly adaptations targeting the RNA polymerase enzyme, pyrimidine metabolism, and ABC transporters, among others.
Advisors:Gagneux, Sebastien and Segata, Nicola
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Ecology and Evolution Unit (Gagneux)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Thesis
Thesis Subtype:Doctoral Thesis
Thesis no:14412
Thesis status:Complete
Number of Pages:174
Identification Number:
  • urn: urn:nbn:ch:bel-bau-diss144128
edoc DOI:
Last Modified:12 May 2022 01:30
Deposited On:02 Nov 2021 16:02

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