Date of Award

5-1-2021

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Biomedical Sciences

Content Description

1 online resource (viii, 99 pages) : illustrations (chiefly color)

Dissertation/Thesis Chair

Pallavi Dr. Ghosh

Committee Members

Todd Dr. Gray, Anil Dr. Ojha

Keywords

antibiotic resistance, HelR, Mab3189c, Mycobacterium abcessus, Rifampicin, Rifampin, Mycobacteria, Drug resistance in microorganisms, Antibiotics, Transcription factors, Tuberculosis, Mycobacteriaceae, Transcription Factors

Subject Categories

Genetics | Microbiology | Molecular Biology

Abstract

Mycobacterium abscessus (Mab), a non-tuberculous environmental mycobacterium is one of the emerging pathogens. The number of Mab infections has doubled in the past decade. It is also an opportunistic pathogen usually infecting immunocompromised individuals and causing numerous skin and soft tissue infections. It commonly causes lung infections in people who are already infected with one or other lung infections such as tuberculosis. The treatment of Mab infections is difficult because of its intrinsic resistance to most of the antibiotics available. This project studies Rifampicin (RIF) resistance in Mab, as RIF is a well-established treatment for other mycobacterial infections including tuberculosis, but Mab is highly resistant towards it. This project aims at understanding RIF resistance in Mab. One of the mechanisms by which Mab shows resistance is by producing RIF inactivating enzymes. Mab_0591/arr has been characterized as one such gene that encodes ADP-Ribosyl transferase that modifies RIF, rendering it ineffective. During the preliminary studies in the lab, another gene Mab_3189c was identified that was highly induced in presence of RIF, suggesting its role in RIF resistance. This project studies Mab3189c, a putative helicase which is the first helicase to be described to confer antibiotic resistance. The study of the basic characteristics of this protein during the project helped us to describe a mechanism of RIF resistance in Mab that is independent of Mab¬_arr and establish the basis for a detailed mechanistic study of this helicase in future. During the project, we also identified Rifampicin associated element (RAE) which is described as a 19bp inverted repeat motif and is recognized in the upstream region of numerous RIF- inactivating enzymes all over genera Actinomycetes. We also discovered RAE in the upstream region of Mab_arr ¬ and Mab¬_3189c which led us to hypothesize that this RAE element is required for transcription of these RIF inactivating genes and thus aim at finding the transcriptional factor/s that bind to it. The identification of the transcriptional factor/s can help in the development of better treatment for Mab infections.

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