Characterization of Drug Resistance in Mycobacterium Tuberculosis via Saturating Mutagenesis of Drug Targets: A Master’s Thesis
Authors
Harris, Michelle J.Faculty Advisor
Jon Goguen, Ph.D.Academic Program
Immunology and MicrobiologyUMass Chan Affiliations
Microbiology and Physiological SystemsDocument Type
Master's ThesisPublication Date
2012-06-15Keywords
Mycobacterium tuberculosisDrug Resistance
Bacterial
Tuberculosis
Multidrug-Resistant
Bacteria
Bacterial Infections and Mycoses
Immunology and Infectious Disease
Life Sciences
Medicine and Health Sciences
Microbiology
Pharmaceutical Preparations
Therapeutics
Metadata
Show full item recordAbstract
Mycobacterium tuberculosis isolates from multiple drug resistant or extensively drug resistant patients show a particular set of mutations in drug targets conferring resistance. However, the selection of drug-resistant strains in vitro yields an alternative set of mutations, thought to result from the cost-benefit associated with drug resistance. Mutations allowing for survival under antibiotic may not be beneficial when presented with the host environment or with a drug-free environment. These fitness effects drive the natural evolution of this bacterium. Using recombineering a large cohort of mutations was generated within two drug targets, inhA and gyrA, to study in vitro the variability of mutations allowable under either isoniazid or ofloxacin, respectively. As a proof of concept this process was carried out in Mycobacterium smegmatis. Analysis of survivors allowed for identification of novel mutations and substitutions, as well as showing mutations previously found only in clinical isolates can be present in laboratory isolates.DOI
10.13028/g58w-0z78Permanent Link to this Item
http://hdl.handle.net/20.500.14038/31952Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/g58w-0z78