Keywords

Two-component system (TCS), Mycobacterium abscessus, phenotypic characterization, genetic engineering, non-tuberculous mycobacteria (NTM), antibiotic resistance

Abstract

Mycobacterium abscessus (Mab) is an emerging pathogen within the nontuberculous bacteria (NTM) which poses a threat due to its complex multi-drug resistance and opportunistic nature. It is predicted that only 45.6% of patients will have successful treatment, with immunocompromised and cystic fibrosis patients being the most threatened. Moreover, investigating new treatment approaches is key to responding to this public health issue. Two-component systems (TCS) are regulatory pathways that play a pivotal role in bacterial survival and virulence. These systems are composed of a sensor histidine kinase (HK) and cognate response regulator (RR) protein that senses environmental cues and triggers specific transcriptional changes to adapt to host-derived cues and stresses. There are eleven complete TCS in Mab, all but one with an ortholog in Mycobacterium tuberculosis (Mtb), however, despite belonging to the same genus, our data suggests that these regulatory systems have diverged to fulfill distinct roles. In this study, genetic engineering methods were implemented, including gene knockout (KO) and CRISPR mediated interference (CRISPRi) to evaluate the role of TCS in Mab gene expression and virulence-associated phenotypes. Phenotypic screening was completed through disk diffusion assays and MIC curves to gain insight into functional roles of TCS in Mab. These findings contribute to setting a foundation for further advancement in mycobacterial research while also identifying potential new drug targets and treatment strategies

Thesis Completion Year

2025

Thesis Completion Semester

Spring

Thesis Chair

Rohde, Kyle

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Thesis Discipline

Biotechnology

Language

English

Access Status

Open Access

Length of Campus Access

None

Campus Location

Orlando (Main) Campus

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Rights Statement

In Copyright