Identification of a small molecule that modifies MglA/SspA interaction and impairs intramacrophage survival of Francisella tularensis.

ABSTRACT: The transcription factors MglA and SspA of Francisella tularensis form a heterodimer complex and interact with the RNA polymerase to regulate the expression of the Francisella pathogenicity island (FPI) genes. These genes are essential for this pathogen's virulence and survival within host cells. In this study, we used a small molecule screening to identify quinacrine as a thermal stabilizing compound for F. tularensis SCHU S4 MglA and SspA. A bacterial two-hybrid system was used to analyze the in vivo effect of quinacrine on the heterodimer complex. The results show that quinacrine affects the interaction between MglA and SspA, indicated by decreased β-galactosidase activity. Further in vitro analyses, using size exclusion chromatography, indicated that quinacrine does not disrupt the het

SUBMITTER: Wrench AP 

PROVIDER: S-EPMC3553074 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature