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Etude fonctionnelle d’un système toxine-antitoxine de type I exprimé par Staphylococcus aureus et d’ARN régulateurs associés aux ribosomes bactériens

Abstract : Staphylococcus aureus is a major human pathogen responsible for nosocomial and community-acquired diseases. With the excessive use of antibiotics, incidence and emergence of multidrug-resistant strains of S. aureus have rapidly increased over the last decade and constitute a serious public health concern. The success of S. aureus as a pathogen is due to its ability to adapt quickly to new environment and to produce an arsenal of virulence factors whose expressions are regulated by proteins and regulatory RNA (regRNA). During my PhD thesis, we showed that RNAs sprG1 and SprF1 constitute a functional type I toxin-antitoxin system (TAS) where sprG1 encodes two toxic peptides. During normal growth conditions, toxin expression is regulated by the antitoxin SprF1 at transcriptional and/or post-transcriptional and translational level, allowing the pathogen to grow. Conversaly, when bacteria are confronted to global nutritive starvation, the antitoxin expression is repressed. This allows accumulation of the sprG1 toxin in cell and translation of both toxic peptides, PepG144 and PepG131, responsible for bacterial stasis. Interestingly, both secreted peptides are able to lyse competitor bacteria in the medium and human erythrocytes. We also showed that upon hyperosmotic stress, SprF1 directly binds ribosomes, probably though one or two ribosome-binding sites, to regulate overall protein synthesis and promote S. aureus persistence. These results suggest that SprF1 belongs to the new emerging class of regRNA regulating translation by direct ribosome-binding. The sprG1/SprF1 TAS is the first example of type I TAS where antitoxin is the leading player of the biological function.
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Régine Brielle. Etude fonctionnelle d’un système toxine-antitoxine de type I exprimé par Staphylococcus aureus et d’ARN régulateurs associés aux ribosomes bactériens. Médecine humaine et pathologie. Université Rennes 1, 2016. Français. ⟨NNT : 2016REN1B037⟩. ⟨tel-01691695⟩

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