ORCID Identifier(s)

ORCID 0000-0001-6598-8644

Graduation Semester and Year

Spring 2024



Document Type


Degree Name

Doctor of Philosophy in Quantitative Biology



First Advisor

Cara Boutte

Second Advisor

Todd Castoe

Third Advisor

Melissa Walsh

Fourth Advisor

Joseph Boll

Fifth Advisor

Mark Pellegrino


Mycobacteria encompass many pathogenic species known to cause severe disease in humans. A well-known example is Mycobacterium tuberculosis (Mtb), the causative agent of the lung disease tuberculosis, which kills millions of humans worldwide yearly. Pathogenic mycobacteria like Mtb are challenging to treat because of their innate ability to adapt to environmental stress. Their unique cell physiology and conserved stress responses allow them to combat biological insults, regulate growth, and regulate genes involved in stress; all these responses increase tolerance to antibiotics. The current therapies to treat mycobacterial infections are lengthy and, at times, unsuccessful, partly due to antibiotic tolerance. A better understanding of mycobacteria cell physiology and stress response will promote the development of better treatments for chronic and recurring antibiotic-tolerant infections. Here, our work focuses on three important aspects of mycobacterial cell biology often associated with survival and antibiotic tolerance: the stringent response (a conserved stress response in bacteria), biofilm formation, and cell wall regulation. We used Mycobacterium abscessus (Mab), a pathogen that causes soft tissue and respiratory infections, for stringent response and biofilm studies. We found that media composition affects the structure and composition of Mab biofilms, and the susceptibility of planktonic cells to antibiotics. In addition, we also discovered that Mab's stringent response pathway uses a non-canonical alarmone synthesis pathway. To study cell wall regulation, we used Mycobacterium smegmatis, a fast-growing non-pathogenic species commonly used to study the Mycobacterium genus. We focused on investigating the relationship between two essential growth proteins, CwlM and MurA, which are involved in the metabolism of the peptidoglycan layer, the primary layer in mycobacteria that provides shape and rigidity. We found that the ix interaction between MurA (the enzyme) and CwlM (its regulator) is transient. We also identified the likely interaction site between CwlM and MurA, which affects the production of precursors by MurA. In addition, we investigated the survival and cell physiology of interaction site mutants, which shed light into understanding the role of CwlM's regulation of MurA during mycobacterial growth.


Mycobacteria, cell wall, peptidoglycan, stress response, biofilms, mycobacterium abscessus, mycobacterium smegmatis, mycobacterium tuberculosis, antibiotic tolerance, gene regulation, phosphorylation


Amino Acids, Peptides, and Proteins | Bacteria | Bacterial Infections and Mycoses | Bacteriology | Enzymes and Coenzymes | Epidemiology | Integrative Biology | Lipids | Microbial Physiology | Molecular Genetics | Pathogenic Microbiology


Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.



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