Staff member

Lucas Pedraz López

PhD Student
Bacterial Infections: Antimicrobial Therapies
+34 934 034 678
Staff member publications

Urrea, L., Segura-Feliu, M., Masuda-Suzukake, M., Hervera, A., Pedraz, L., Aznar, J. M. G., Vila, M., Samitier, J., Torrents, E., Ferrer, I., Gavín, R., Hagesawa, M., Del Río, J. A., (2017). Involvement of cellular prion protein in Molecular Neurobiology online, 1-14

The cellular prion protein, encoded by the gene Prnp, has been reported to be a receptor of

Keywords: Amyloid spreading, Microfluidic devices, Prnp, Synuclein

Crespo, Anna, Pedraz, Lucas, Astola, Josep, Torrents, Eduard, (2016). Pseudomonas aeruginosa exhibits deficient biofilm formation in the absence of class II and III ribonucleotide reductases due to hindered anaerobic growth Frontiers in Microbiology 7, Article 688

Chronic lung infections by the ubiquitous and extremely adaptable opportunistic pathogen Pseudomonas aeruginosa correlate with the formation of a biofilm, where bacteria grow in association with an extracellular matrix and display a wide range of changes in gene expression and metabolism. This leads to increased resistance to physical stress and antibiotic therapies, while enhancing cell-to-cell communication. Oxygen diffusion through the complex biofilm structure generates an oxygen concentration gradient, leading to the appearance of anaerobic microenvironments. Ribonucleotide reductases (RNRs) are a family of highly sophisticated enzymes responsible for the synthesis of the deoxyribonucleotides, and they constitute the only de novo pathway for the formation of the building blocks needed for DNA synthesis and repair. P. aeruginosa is one of the few bacteria encoding all three known RNR classes (Ia, II, and III). Class Ia RNRs are oxygen dependent, class II are oxygen independent, and class III are oxygen sensitive. A tight control of RNR activity is essential for anaerobic growth and therefore for biofilm development. In this work we explored the role of the different RNR classes in biofilm formation under aerobic and anaerobic initial conditions and using static and continuous-flow biofilm models. We demonstrated the importance of class II and III RNR for proper cell division in biofilm development and maturation. We also determined that these classes are transcriptionally induced during biofilm formation and under anaerobic conditions. The molecular mechanism of their anaerobic regulation was also studied, finding that the Anr/Dnr system is responsible for class II RNR induction. These data can be integrated with previous knowledge about biofilms in a model where these structures are understood as a set of layers determined by oxygen concentration and contain cells with different RNR expression profiles, bringing us a step closer to the understanding of this complex growth pattern, essential for P. aeruginosa chronic infections.

Keywords: Pseudomonas aeruginosa, Ribonucleotide Reductases, Vitamin B 12, Anaerobic metabolism, Biofilm formation, DNA Synthesis, Oxygen diffusion, nrd genes.

Pedraz, Lucas, Crespo, Anna, Torrents, Eduard, (2016). A single transcription factor behind all bacterial dNTP synthesis revealed as a novel antimicrobial target New Biotechnology Biotech Annual Congress (BAC 2015) , Elsevier (Salamanca, Spain) 33, (3), 410

Nowadays, the fear of infectious diseases is again increasing. Antibiotic-resistant bacterial strains are appearing worldwide, and so there is an urgent need to develop new antimicrobial drugs. Ribonucleotide Reductases (RNRs) are essential enzymes that catalyse the reduction of ribonucleotides (NTPs) to their corresponding deoxyribonucleotides (dNTPs), thereby forming the building blocks for DNA synthesis and repair. A drug able to inhibit bacterial Ribonucleotide Reductase activity would completely inhibit bacterial growth. Behind bacterial Ribonucleotide Reductase activity there is a complex regulon; although eukaryotic cells codify only for one RNR enzyme, bacteria can use three different RNR classes, granting them a huge adaptability. Pseudomonas aeruginosa is a major human opportunistic pathogen, causing severe lung chronic infections in cystic fibrosis and COPD patients. It codifies for all three RNR classes, in a complex regulon necessary for its adaptability and virulence. The main focus of this work is a transcription factor, called NrdR, which is present in almost all bacterial species, and completely absent in eukaryotic organisms. This factor acts as a central regulator of all RNR enzymes in bacteria, hence being behind all dNTP synthesis. We have studied how NrdR regulates RNR activity in P. aeruginosa, being able to this point to propose a first model of the NrdR regulon, and being a step closer to new antimicrobial therapies.

Crespo, A., Pedraz, L., Torrents, E., (2015). Function of the Pseudomonas aeruginosa NrdR transcription factor: Global transcriptomic analysis and its role on ribonucleotide reductase gene expression PLoS ONE 10, (4), e0123571

Ribonucleotide reductases (RNRs) are a family of sophisticated enzymes responsible for the synthesis of the deoxyribonucleotides (dNTPs), the building blocks for DNA synthesis and repair. Although any living cell must contain one RNR activity to continue living, bacteria have the capacity to encode different RNR classes in the same genome, allowing them to adapt to different environments and growing conditions. Pseudomonas aeruginosa is well known for its adaptability and surprisingly encodes all three known RNR classes (Ia, II and III). There must be a complex transcriptional regulation network behind this RNR activity, dictating which RNR class will be expressed according to specific growing conditions. In this work, we aim to uncover the role of the transcriptional regulator NrdR in P. aeruginosa. We demonstrate that NrdR regulates all three RNR classes, being involved in differential control depending on whether the growth conditions are aerobic or anaerobic. Moreover, we also identify for the first time that NrdR is not only involved in controlling RNR expression but also regulates topoisomerase I (topA) transcription. Finally, to obtain the entire picture of NrdR regulon, we performed a global transcriptomic analysis comparing the transcription profile of wild-type and nrdR mutant strains. The results provide many new data about the regulatory network that controls P. aeruginosa RNR transcription, bringing us a step closer to the understanding of this complex system.

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