Neisseria gonorrhoeae, Escherichia coli and Staphylococcus aureus are considered by CDC to be urgent health threats and are classified by WHO as high priority pathogens for R&D of new antibiotics. Our lab aims to identify and characterize enzymes as new drug targets, which will have an impact on both the health care system and society.
Thus, we investigate molecular systems responsible for the detoxification of ROS and metal tolerance from pathogenic bacteria, which are a strategy used by these bacteria to evade the human immune system. For that we use spectroscopic and biophysical techniques, steady-state kinetics, complemented by proteomics and transcriptomic analysis. Biomolecular NMR and molecular docking are used to structurally characterize the proteins and their complexes.
How pathogenic bacteria deal with ROS, RNS and metal stress?
Bacterial Peroxidases are periplasmic enzymes involved in the reduction of hydrogen peroxide in the periplasm of pathogenic bacteria, and are considered to be a first line defence mechanism against hydrogen peroxide during infection.
The di-heme bacterial peroxidase from N. gonorrhoeae was spectroscopic and biochemically characterized, and shown to receive electrons from the lipid modified azurin from the same organism. The tri-heme bacterial peroxidase from E. coli was isolated and biochemically characterized for the first time. This enzyme is a quinol peroxidase that is expressed under anaerobic conditions, and is considered to be involved in a respiratory chain using hydrogen peroxide as terminal electron acceptor.
- “Detoxification of hydrogen peroxide by Pathogenic bacteria - E. coli tri-haem peroxidase as a model (PathG_CCP)”, FCT-MCTES, Total and Unit funding: € 237,634, Sofia R. Pauleta (PI).
- “The Biogenesis of Iron-sulfur Proteins: from Cellular Biology to Molecular Aspects (FeSBioNet)” - Cost Action CA15133, Sofia R. Pauleta: substitute MC & Communication´s Representative.
- “Understanding and Exploiting the Impacts of Low pH on Micro-Organisms (FesBio)” - Cost Action CA18113, Sofia R. Pauleta: National Management Committee Member.
- “Functional and structural characterization of unknown function conserved metalloproteins in anaerobes: a putative role in the control of cell division?”, FCT-MCTES, Total and Unit funding: € 225.280.00, Sofia R. Pauleta (PI).
- “The metalloproteins involved in cell division - Functional and Structural Characterization”, Pessoa 2014 between REQUIMTE and CNRS, Total funding: €2,000 Sofia R. Pauleta (PI).
- “Insights into novel bacterial cytochrome c peroxidases from pathogenic bacteria, Neisseria gonorrhoeae and Escherichia coli”, FCT-MCTES, Total and Unit funding: € 191,979, Sofia R. Pauleta (PI).
Pauleta, Sofia R.; Grazina, Raquel; Carepo, Marta S. P.; Moura, José J. G.; Moura, Isabel. 2023. Iron-sulfur clusters – functions of an ancient metal site. Chemistry, Molecular Sciences and Chemical Engineering, DOI: 10.1016/b978-0-12-823144-9.00116-3
Daniela S. Barreiro and Ricardo N. S. Oliveira and Sofia R. Pauleta. 2022. Biochemical characterization of AniA from Neisseria gonorrhoeae. bioRxiv, DOI: 10.1101/2022.04.07.487406
Fievet, A; Merrouch, M; Brasseur, G; Eve, D; Biondi, EG; Valette, O; Pauleta, SR; Dolla, A; Dermoun, Z; Burlat, B; Aubert, C. 2021. OrpR is a sigma(54)-dependent activator using an iron-sulfur cluster for redox sensing in Desulfovibrio vulgaris Hildenborough. MOLECULAR MICROBIOLOGY, DOI: 10.1111/mmi.14705
André G.Favinha, Daniela S.Barreiro, Joana N.Martins, PhilipO'Toole, Sofia R.Pauleta. 2020. Acrylamide-hemoglobin adduct: A spectroscopic study. SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY, 241, DOI: 10.1016/j.saa.2020.118644
Carreira, C; Nunes, RF; Mestre, O; Moura, I; Pauleta, SR. 2020. The effect of pH on Marinobacter hydrocarbonoclasticus denitrification pathway and nitrous oxide reductase. JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY, DOI: 10.1007/s00775-020-01812-0
Carreira, C; dos Santos, MMC; Pauleta, SR; Moura, I. 2020. Proton-coupled electron transfer mechanisms of the copper centres of nitrous oxide reductase from Marinobacter hydrocarbonoclasticus – An electrochemical study. BIOELECTROCHEMISTRY, 133, DOI: 10.1016/j.bioelechem.2020.107483
Pauleta, SR; Carepo, MSP; Moura, I. 2019. Source and reduction of nitrous oxide. COORDINATION CHEMISTRY REVIEWS, 387, DOI: 10.1016/j.ccr.2019.02.005
Cláudia S. Nóbrega, Sofia R. Pauleta. 2019. Reduction of hydrogen peroxide in gram-negative bacteria – bacterial peroxidases. Advances in Microbial Physiology, 74, DOI: 10.1016/bs.ampbs.2019.02.006