Dissertations, Theses, and Capstone Projects
Date of Degree
2-2023
Document Type
Dissertation
Degree Name
Ph.D.
Program
Biology
Advisor
Luis E.N. Quadri
Committee Members
Theodore Muth
Juergen Polle
Peter Lipke
Venkatesan Jayaprakash
Subject Categories
Bacterial Infections and Mycoses | Bacteriology | Biology | Diseases | Microbiology | Molecular Biology | Molecular Genetics | Pathogenic Microbiology
Keywords
mycobacteria, Mycobacterium abscessus, Mycobacterium tuberculosis, iron, ESX-3, siderophores
Abstract
The opportunistic pathogen Mycobacterium abscessus subsp. abscessus (Mab) has become an emerging public health threat due to the increasing number of Mab-associated chronic pulmonary disease cases. Infection cure rates are only 50% due to the complex resistance of Mab to most antimicrobial drugs and chemotherapy.
Deeper knowledge of Mab biology is needed to illuminate potential candidates for development of improved therapeutics against Mab infections. The ESX-3 type VII protein secretion system of Mab plays an important role in host inflammatory and pathological responses during infection.
In this study, we demonstrate a functional link between the ESX-3 secretion system and an iron uptake system based on an unusual mycobactin-type siderophore (designated MBT Ab), and exploit this link to implement a large genetic screen for transposon mutants with an impaired ESX-3. Most mutants we identified carry insertions in genes encoding predicted ESX-3 secretion machinery components or potential ESX-3 substrates.
The mutant isolates overproduce MBT Ab, a trait consistent with an iron uptake defect. To determine whether MAB_2247c gene expression, a putative homolog of Mycobacterium tuberculosis mbtA gene located in the mbt gene cluster, is related to the synthesis of MBT Ab under iron deprivation conditions, we created a targeted Mab mbtA deletion mutant. The collection of novel mutants generated in this study will facilitate future research to better understand the role of the ESX-3 secretion system and its interplay with the siderophore system.
Recommended Citation
Farhat, Manal F., "Genetic Determinants Involved in Acquisition of Iron in the Opportunistic Pathogen Mycobacterium abscessus" (2023). CUNY Academic Works.
https://academicworks.cuny.edu/gc_etds/5139
Graduate Center users:
To read this work, log in to your GC ILL account and place a thesis request.
Non-GC Users:
See the GC’s lending policies to learn more.
Included in
Bacterial Infections and Mycoses Commons, Bacteriology Commons, Biology Commons, Molecular Biology Commons, Molecular Genetics Commons, Pathogenic Microbiology Commons