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Chemistry Colloquium: A big role for a small RNA: Protection from a self-lethal protein by a small RNA in the pathogenic bacterium Shigella flexneri

Professor Erin Murphy will be the guest speaker for the Chemistry & Biochemistry Collquium. Dr. Murphy is Chair of Biomedical Sciences and Professor of Bacteriology in the Heritage College of Osteopathic Medicine, Ohio University.

 

Bacterial toxin-antitoxin systems are typically composed of two genetically linked factors, a stable self-lethal toxin and a labile antitoxin that functions to protect against the activity of the cognate toxin. Initially implicated in antibiotic resistance, stress response, and persistence, there is growing evidence that chromosomally encoded bacterial toxin-antitoxin systems are doing more than mediating growth inhibition and cell death, and that these systems are more versatile than initially thought. The high level of variability in function, mechanism, and regulation seen even among related toxin-antitoxin systems has led the field to recognize the importance of comprehensive experimental characterization of individual systems. Our current studies are focused on the Ryf toxin-antitoxin system in Shigella flexneri, an important medically relevant bacterial pathogen categorized as a Category B Emerging Pathogen by the National Institutes of Health. Partially conserved among Shigella species and other related bacterial pathogens, the S. flexneri ryf locus is unique in that it encodes three components rather than two, one toxin (RyfA) and two potential antitoxins (RyfB and RyfB1). Initially identified as a “toxic RNA”, evidence now suggests that the RyfA toxin functions as a small peptide whose production is specifically controlled by the activity of RyfB, a regulatory small RNA. Many fundamental questions remain regarding the ryf system and others like it. These studies aim to address these questions by investigating the molecular mechanism controlling the production and activity of each component of the Ryf system. Harnessing the self-lethal activity of bacterial toxin-antitoxin systems has the potential to specifically eliminate an invading pathogen, a potential that cannot be realized until their function(s), mechanism(s) of action, and regulation are fully characterized.

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