Light regulates virulence in Brucella abortus by a LOV-domain histidine kinase protein.

PARIS, GASTON; DIEGO J. COMERCI; TREVOR E. SWARTZ; WINSLOW R. BRIGGS; ROBERTO A. BOGOMOLNI; RODOLFO A. UGALDE; FERNANDO A. GOLDBAUM

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular.; 2007

Brucella abortus is a facultative intracellular pathogen that causes brucellosis in animals and humans. B. abortus contains a LOV-histidine kinase (LOV-HK) protein. LOV domains are light sensory modules that bind FMN and undergo a self-contained photocycle that is dependent on the presence of a conserved cys residue. Upon illumination the cys forms a covalent bond between the sulfur and C4a carbon of FMN. To investigate the in vivo function of Brucella LOV-HK a knocked-out null mutant was obtained. Cell infection assays of macrophages showed that LOV-HK mutant strain has an attenuated phenotype as compared with the wild type. A complemented strain expressing the LOV-HK gene in LOV-HK mutant strain was able to rescue the phenotype. However, a LOV-HK C69A replacement which cannot form the covalent adduct showed the same infection profile that the LOV-HK knockout strain, indicating that formation of covalent adduct is essential for its biological activity. To determine if LOV-HK functions as photoreceptor during host-pathogen interactions, the infection experiment was performed in light vs. dark conditions. Strikingly, the number of wild type intracellular bacteria recovered from the culture kept in the dark was roughly one order of magnitude less than in the light-treated culture, moreover, no difference between dark and light conditions was detected with the LOV-HK knockout mutant.