Bacteria commonly use two-component sensors to sense and respond to their environment. The Gram-negative opportunistic pathogen Pseudomonas aeruginosa has one of the largest sets of two-component sensors known in bacteria, which likely contributes to its ability to adapt to diverse environments, including the human host. Several of these sensors such as GacS have been shown to play a role in the regulation of virulence in this pathogen. However, the role of the majority of sensors remains unknown. In this thesis I show that the two-component sensor KinB is required for full P. aeruginosa virulence in the recently characterized model host Danio rerio. I found that KinB regulates several virulence-associated phenotypes in P. aeruginosa including pyocyanin and elastase production and motility. I show that KinB regulates these phenotypes through the global sigma factor AlgU, which plays a critical role in the repression of P. aeruginosa acute virulence factors and through its cognate response regulator, AlgB, albeit in a non-canonical manner. KinB’s primary role in the regulation of acute virulence is to act as a phosphatase to dephosphorylate AlgB.