Journal
SCIENTIFIC REPORTS
Volume 7, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-017-17917-7
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Funding
- Spanish Ministerio de Economia y Competitividad (MINECO/FEDER) [BFU2011-24066, BIO2015-63557-R]
- Generalitat de Catalunya [2014 SGR01260]
- Generalitat de Catalunya (CERCA programme)
- Catalan Cystic Fibrosis foundation
- Spanish Cystic Fibrosis foundation
- La Caixa Foundation
- Ministerio de Economia y Competitividad
- Generalitat de Catalunya through the FI program [2015-FI-B-00817]
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Ribonucleotide reductases (RNR) catalyze the last step of deoxyribonucleotide synthesis, and are therefore essential to DNA-based life. Three forms of RNR exist: classes I, II, and III. While eukaryotic cells use only class Ia RNR, bacteria can harbor any combination of classes, granting them adaptability. The opportunistic pathogen Pseudomonas aeruginosa surprisingly encodes all three classes, allowing it to thrive in different environments. Here we study an aspect of the complex RNR regulation whose molecular mechanism has never been elucidated, the well-described induction through oxidative stress, and link it to the AlgZR two-component system, the primary regulator of the mucoid phenotype. Through bioinformatics, we identify AlgR binding locations in RNR promoters, which we characterize functionally through EMSA and physically through AFM imaging. Gene reporter assays in different growth models are used to study the AlgZR-mediated control on the RNR network under various environmental conditions and physiological states. Thereby, we show that the two-component system AlgZR, which is crucial for bacterial conversion to the mucoid phenotype associated with chronic disease, controls the RNR network and directs how the DNA synthesis pathway is modulated in mucoid and non-mucoid biofilms, allowing it to respond to oxidative stress.
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