The lactoperoxidase (LPO) antimicrobial system has been shown to play an important role in maintaining sterile conditions in several tissues including the mammary gland, the salivary gland, and the airway. The LPO system in the airway consists of the enzyme LPO and its substrates hydrogen peroxide and an anion. LPO catalyzes the oxidation of a halide or pseudohalide ion for example SCN-or I- by hydrogen peroxide producing a product, OSCN- or OI- which have antibacterial, antifungal, and antiviral properties. In order to have a functional antimicrobial system all the components need to be present at appropriate concentrations. The LPO system has been suggested to be deficient in cystic fibrosis. There are three possible regulatory mechanism of this antimicrobial system and these involve the secretion and availability of the three components of the LPO system in the luminal fluid. The studies presented in this dissertation examine two of the possible regulatory mechanisms of the LPO system in the airway; the availability and transport of SCN- to the luminal surface, and the expression of LPO. The knowledge obtained from these studies could be utilized to develop treatments to control infection in diseases characterized by chronic infections such as cystic fibrosis.

Le domaine de la bioénergie moléculaire concerne le transfert et le stockage d’énergie dans les cellules biologiques. Ce projet s’articule autour de la respiration et plus précisément le mécanisme de pompage de sodium et de protons, et son couplage au transfert d’électrons. Premièrement, nous nous sommes intéressés au pompage d’ions sodium par la NADH : quinone oxidoreductase de la bactérie Vibrio cholerae. L’importance de flavines spécifiques et des résidus acides dans le transfert de sodium ont été démontrée. Par la suite, l’interaction entre protéines, notamment le cytochrome c552 et le fragment CuA de l’oxidase de type ba3 de l’organisme Thermus thermophilus a été étudié. Une réorganisation structurelle induit par le transfert d’électron a été démontrée par la spectroscopie IRTF différentielle. Enfin, dans la dernière partie de ce travail, l’interaction au sein du supercomplex bc1-aa3 de la chaîne respiratoire du Corynebacterium glutamicum a été analysée. / The field of molecular bioenergetics deals with the energy transduction in biological cells. In this project, respiration and more specifically proton and sodium pumping enzymes and their coupling to electron transfer have been in focus. First we have been interested in the Na+-pumping NADH:quinone reductase from Vibrio cholerae which is the entry site of electrons in the respiratory chain of several pathogens. The role of specific flavin cofactors and amino acids involved in Na+ transfer has been shown in a combined IR spectroscopic and electrochemical approach. The interaction between proteins, namely the cytochrome c552 and the CuA fragment from the terminal ba3 oxidase from the organism Thermus thermophilus was then investigated. Structural reorganization during electron transfer was revealed by IR spectroscopy. Finally, in the third part of the project the interaction within the bc1-aa3 supercomplex from the respiratory chain from Corynebacterium glutamicum was analyzed.