title: 23S rRNA as an a-Maz-ing new bacterial toxin target.
abstract: Mycobacterium tuberculosis, the causative agent of tuberculosis in humans, is a bacterium with the unique ability to persist for years or decades as a latent infection. This latent state, during which bacteria have a markedly altered physiology and are thought to be dormant, is crucial for the bacteria to survive the stressful environments it encounters in the human host. Importantly, M. tuberculosis cells in the dormant state are generally refractory to antibiotics, most of which target cellular processes occurring in actively replicating bacteria. The molecular switches that enable M. tuberculosis to slow or stop its replication and become dormant remain unknown. However, the slow growth and dormant state that are hallmarks of latent tuberculosis infection have striking parallels to the "quasi-dormant" state of Escherichia coli cells caused by the toxin components of chromosomal toxin-antitoxin (TA) modules. An unusually large number of TA modules in M. tuberculosis, including nine in the mazEF family, may contribute to initiating this latent state or to adapting to stress conditions in the host. Toward filling the gap in our understanding of the physiological role of TA modules in M. tuberculosis, we are interested in identifying their molecular mechanisms to better understand how toxins impart growth control. Our recent publication (1) uncovered a novel function of a MazF toxin in M. tuberculosis that had not been associated with any other MazF ortholog. This toxin, MazF-mt6, can disrupt protein synthesis by cleavage of 23S rRNA at a single location in an evolutionarily conserved five-base sequence in the ribosome active center.
authors: Department of Biochemistry and Molecular Biology; Rutgers University; Robert Wood Johnson Medical School; Piscataway, NJ USA.
authors: Jason M
authors: JM
authors: Schifano
authors: Department of Biochemistry and Molecular Biology; Rutgers University; Robert Wood Johnson Medical School; Piscataway, NJ USA.
authors: Nancy A
authors: NA
authors: Woychik
mesh_terms: D000222:Adaptation, Physiological; D000992:Antitoxins / Q000235:genetics / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000378:metabolism*; D001483:Base Sequence; D001665:Binding Sites; D017124:Conserved Sequence; D019143:Evolution, Molecular; D005798:Genes, Bacterial; D006801:Humans; D008957:Models, Genetic; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000378:metabolism*; D009876:Operon; D012329:RNA, Bacterial / Q000235:genetics; D012338:RNA, Ribosomal, 23S / Q000378:metabolism*; D012270:Ribosomes / Q000378:metabolism
chemical_list: D000992:Antitoxins; D001427:Bacterial Toxins; D012329:RNA, Bacterial; D012338:RNA, Ribosomal, 23S
keywords: antitoxin; endoribonuclease; protein synthesis; ribosome; tuberculosis