Research

 

We focus our studies on Salmonella enterica serovar Typhimurium, which is the etiologic agent of gastroenteritis in humans and causes in mice a typhoid fever-like disease. We investigate the determinants that allow Salmonella to prosper in host tissues as well as those mediating the adaptation to conditions that are limiting in Mg2+, which is the most abundant divalent cation in biological systems.

GENETIC NETWORKS CONTROLLING VIRULENCE
We are investigating the PhoP/PhoQ system, which is the major regulator of virulence functions and magnesium homeostasis in Salmonella. This system consists of the Mg2+ sensor PhoQ, which modifies the activity of the DNA-binding regulatory protein PhoP. Certain genes are directly controlled by PhoP whereas others are regulated indirectly, via different types of regulatory cascades. One such cascade is the one mediated by the PhoP-activated PmrD protein, which activates the PmrA/PmrB system at a post-translational level, whereas another one controls the SpiR/SsrB system at post-transcriptional and transcriptional levels.

 

CELL ENVELOPE MODIFICATIONS AFFECTING THE INTERACTION WITH HOST MOLECULES
We examine the contribution that the PhoP-regulated cell envelope modifications make to an organism’s ability to prosper within mammalian tissues, to resist killing by antimicrobial peptides, to alter the host immune response, and to survive environments that are limiting in magnesium.

COMPARATIVE GENOMICS OF BACTERIAL REGULONS
We explore the genetic networks controlled by homologous two-component systems in related bacterial species. We are interested in understanding how different network designs determine the niches that different organisms can occupy.