IDENTIFICATION OF A PLANT EXTRACT WITH INHIBITORY ACTIVITY AGAINST Salmonella enterica PhoP/PhoQ SYSTEM

VIARENGO, GASTÓN; SALAZAR, MARIO O.; FURLÁN, RICARDO L. E.; GARCÍA VÉSCOVI, ELEONORA

Potrero de los Funes, San Luis

Congreso; 47th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2011

Salmonella is an enteropathogen that causes a wide range of diseases in humans and animals. During infection, bacteria continuously interact with the surrounding media, in order to coordinate the expression of genes required for invasion and colonization of the host. In S. typhimurium, the PhoP/PhoQ two-component system (TCS) controls the virulence, the adaptation to limited Mg2+ conditions and the resistance to antimicrobial peptides. Because mammals lack TCS, histidine kinases might be strategic targets for new antimicrobial agents. By using a bioguided strategy, consisting on a TLC-overlay with a strain carrying a PhoP-controlled reporter gene, we have determined that a purified fraction from a Lamium amplexicaule methanol extract represses the PhoP/PhoQ system, but has no effect on genes regulated by other homologous and heterologous systems. This was confirmed by quantitative -galactosidase activity assays. Using membrane vesicles enriched in the sensor protein we have also established that the target of action is the autokinase activity of PhoQ, and that the response is dose-dependent. Further studies are being carried out in order to determine the specificity of the inhibition and the molecular basis for this action. This methodology stands for a new strategy for the search and identification of antimicrobial agents in plants.