A Novel Mutagenic Screen Reveals A Model For Interaction Between The Biofilm Regulatory Proteins NspS And MbaA In Vibrio Cholerae

The transition between motility and biofilm formation is important to the lifecycle of the human pathogen Vibrio cholerae, which causes the disease cholera. Polyamines are ubiquitous, organic molecules and an example of one environmental signal that play a role in the regulation of V. cholerae biofilm formation. V. cholerae detects polyamines through a putative signaling pathway composed of a periplasmic protein, NspS, and a transmembrane protein, MbaA. Previous studies have determined that the cytoplasmic EAL domain of MbaA has phosphodiesterase (PDE) activity and can break down c-di-GMP, which positively regulates biofilm formation. In this pathway, NspS bound by a polyamine is hypothesized to interact with the periplasmic domain of MbaA to alter the PDE activity of the EAL domain dependent on the polyamine bound. Altering this activity of MbaA is thought to modify levels of c-di-GMP, affecting biofilm formation. The purpose of this study was to determine the potential binding surface on NspS that interacts with the periplasmic domain of MbaA. Based on the results, I present a model of this interaction in which NspS interacts with the periplasmic domain of MbaA to alter its PDE activity and regulate biofilm formation in response to polyamines in the environment.