Streptococcus agalactiae adapts to glucose stress conditions by modulating gene expression profile

Di Palo, Benedetta (2012) Streptococcus agalactiae adapts to glucose stress conditions by modulating gene expression profile, [Dissertation thesis], Alma Mater Studiorum Università di Bologna. Dottorato di ricerca in Biologia cellulare, molecolare e industriale/cellular, molecular and industrial biology: progetto n. 2 Biologia funzionale dei sistemi cellulari e molecolari, 24 Ciclo. DOI 10.6092/unibo/amsdottorato/4805.
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Diabetes mellitus is considered a risk factor for Group B Streptococcus (GBS) infections. Typically, this pathology is associated to high glucose levels in the bloodstream. Although clinical evidences support this notion, the physiological mechanisms underlying GBS adaptation to such conditions are not yet defined. In the attempt to address this issue, we performed comparative global gene expression analysis of GBS grown under glucose-stress conditions and observed that a number of metabolic and virulence genes was differentially regulated. Of importance, we also demonstrated that by knocking-out the csrRS locus the transcription profile of GBS grown in high-glucose conditions was profoundly affected, with more than a third of glucose-dependent genes, including the virulence factor bibA, found to be controlled by this two-component system. Furthermore, in vitro molecular analysis showed that CsrR specifically binds to the bibA promoter and the phosphorilation increases the affinity of the regulator to this promoter region. Moreover, we demonstrated that CsrR acts as a repressor of bibA expression by binding to its promoter in vivo. In conclusion, this work by elucidating both the response of GBS to pathological glucose conditions and the underlined molecular mechanisms will set the basis for a better understanding of GBS pathogenesis.

Tipologia del documento
Tesi di dottorato
Di Palo, Benedetta
Dottorato di ricerca
Scuola di dottorato
Scienze biologiche, biomediche e biotecnologiche
Settore disciplinare
Settore concorsuale
Parole chiave
GBS, CsrRS, BibA
Data di discussione
27 Aprile 2012

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