IDENTIFICATION OF A Streptomyces NATURAL PRODUCT WITH POTENTIAL ANTI-VIRULENCE PROPERTIES

BÁRBARA BERCOVICH; GRAMAJO H; CARABAJAL MA; GARCÍA VÉSCOVI E; BRUNA RE; EDUARDO J. RODRIGUEZ

Paraná, Entre Ríos

Congreso; LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2018

SAIB

Salmonella is an enteropathogen responsible for a wide range of diseases in humans and animals. In S. Typhimurium, the PhoP/PhoQ twocomponentsystem (TCS) controls both adaptation to low Mg2+ environments and key virulent phenotypes. Hence, and considering that TCSsignallingis not present in humans, PhoP/PhoQ constitutes an optimal target for the identification of new compounds with pharmacologicalpotential against Salmonella infections. The aim of this work was to carry out a screening of culture supernatants from a library of Streptomycesspecies -well known for their ability to produce secondary metabolites with clinical value- to identify molecules that could modulate PhoP/PhoQTCS, and therefore inhibit the virulence of S. Typhimurium. 118 Streptomyces strains were grown and their corresponding supernatants weretested against Salmonella strains carrying a lacZ transcriptional reporter fusion to PhoP-activated genes. Samples that significantly repressreporter activity and did not affect Salmonella growth were further analyzed. Highest repression effect was founded for theStreptomyceseurocidicus culture supernatant. Differential solvent organic extractions allowed toanalyze different fractions of this extract byTLC, which were subsequently revealed by bioassays based on the inhibitory activity of PhoP-activated genes. These assays together with apurification of this extract, suggested that a nitroimidazole scaffold is responsible for the repression activity. In sum, we identified a naturallysecreted compound from S. eurocidicus with potential anti-virulence properties over S. Typhimurium.