Ribonucleotide Reductases of Salmonella Typhimurium: Transcriptional Regulation and Differential Role in Pathogenesis

Anaïs Panosa, Ignasi Roca, Isidre Gibert

Research output: Contribution to journalArticleResearchpeer-review

21 Citations (Scopus)

Abstract

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. © 2010 Panosa et al.
Original languageEnglish
Article numbere0011328
JournalPLoS ONE
Volume5
DOIs
Publication statusPublished - 1 Dec 2010

Fingerprint Dive into the research topics of 'Ribonucleotide Reductases of Salmonella Typhimurium: Transcriptional Regulation and Differential Role in Pathogenesis'. Together they form a unique fingerprint.

Cite this