Per citar aquest document: http://ddd.uab.cat/record/112577
Ribonucleotide reductases of Salmonella Typhimurium : transcriptional regulation and differential role in pathogenesis
Panosa Borràs, Anaïs (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Roca Subirà, Ignasi (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Gibert, Isidre (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Data: 2010
Resum: Ribonucleotide reductases (RNRs) are essential enzymes that carry out the de novo synthesis of deoxyribonucleotides by reducing ribonucleotides. There are three different classes of RNRs (I, II and III), all having different oxygen dependency and biochemical characteristics. Salmonella enterica serovar Typhimurium (S. Typhimurium) harbors class Ia, class Ib and class III RNRs in its genome. We have studied the transcriptional regulation of these three RNR classes in S. Typhimurium as well as their differential function during infection of macrophage and epithelial cells. Deletion of both NrdR and Fur, two main transcriptional regulators, indicates that Fur specifically represses the class Ib enzyme and that NrdR acts as a global repressor of all three classes. A Fur recognition sequence within the nrdHIEF promoter has also been described and confirmed by electrophoretic mobility shift assays (EMSA). In order to elucidate the role of each RNR class during infection, S. Typhimurium single and double RNR mutants (as well as Fur and NrdR mutants) were used in infection assays with macrophage and epithelial cell lines. Our results indicate class Ia to be mainly responsible for deoxyribonucleotide production during invasion and proliferation inside macrophages and epithelial cells. Neither class Ib nor class III seem to be essential for growth under these conditions. However, class Ib is able to maintain certain growth in an nrdAB mutant during the first hours of macrophage infection. Our results suggest that, during the early stages of macrophage infection, class Ib may contribute to deoxyribonucleotide synthesis by means of both an NrdR and a Fur-dependent derepression of nrdHIEF due to hydrogen peroxide production and DNA damage associated with the oxidative burst, thus helping to overcome the host defenses.
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès.
Document: article ; publishedVersion
Matèria: Genètica molecular ; Microbiologia ; Transcripció genètica ; Regulació ; Salmonel·la typhimurium ; Mutant strains ; Macrophages ; Fur ; Promoter regions ; Regulator genes
Publicat a: PLoS one, Vol. 5, Issue 6 (June 2010) , p.e11328, ISSN 1932-6203

DOI: 10.1371/journal.pone.0011328


11 p, 784.6 KB

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