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Title Genome scale tracking of Mycobacterium tuberculosis MazF toxin targets
Publication Date
Degree MS
Discipline/Department Microbial Biology
Degree Level masters
University/Publisher Rutgers University
Abstract Mycobacterium tuberculosis, the bacteria that causes tuberculosis (TB), claims millions of lives every year. Due to coinfection of TB and HIV, increasing antibiotic resistance, and the unique ability of M. tuberculosis to persist in a non-replicating state within its host as a latent infection, TB eradication attempts have consistently failed. Latent TB infects one-third of the world’s population and is refractory to many antibiotics, yet the molecular mechanisms by which M. tuberculosis enters and maintains latency are poorly understood. However, members of the MazF family of toxins, which act by cleaving specific regions of single-stranded RNA, are implicated in this process. To help elucidate the role that MazF toxins play in latent tuberculosis, we used a novel RNA-sequencing approach, 5’RNA-seq, to determine the RNA targets of 4 M. tuberculosis MazF toxins. While MazF-mt10 cleaved at a specific consensus sequence, CACCU, MazF-mt4, -mt7, and -mt11 did not appear to cleave at a specific sequence. MazF-mt7 cleaved at a number of positions within 23S rRNA; degradation of 23S rRNA could serve as a potent mechanism by which to inhibit translation and modulate growth. MazF-mt7 and -mt10 cleaved 16S rRNA slightly upstream of the 3’ end, thus removing the anti-Shine-Dalgarno sequence and potentially aiding in the formation of stress ribosomes that can preferentially translate leaderless mRNAs in M. tuberculosis. MazF-mt4, -mt7 and –mt11 cleaved distinct tRNAs at their anticodon stem loop, providing another way through which to regulate translation. Results from this study could lead to the identification of MazF-related biomarkers for latent tuberculosis, which could in turn be used to develop new, more effective antimicrobials to fight latent tuberculosis.
Subjects/Keywords Mycobacterium tuberculosis
Contributors Woychik, Nancy A (chair); Bhattacharya, Debashish (internal member); Boyd, Jeffrey M (internal member); Zylstra, Gerben J (internal member); School of Graduate Studies
Language en
Rights The author owns the copyright to this work.
Country of Publication us
Format 1 online resource (x, 56 p. : ill.)
Record ID oai:example.org:rutgers-lib:55482
Other Identifiers rutgers-lib:55482; ETD_8315
Repository rutgers
Date Indexed 2021-02-13

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