Gram-negative bacteria posses a variety of secretion systems to deliver proteins into the environment; to both manipulate their surroundings and to survive within a mammalian host.  This has lead to a co-evolutionary relationship between the pathogen and its host, which involves a delicate balance of virulence factorsand antivirulence factors.  Bacterial virulence factors can directly manipulate or subvert the molecular pathways of eukaryotic cells for the benefit of the bacterium.  In contrast, bacterial antivirulence factors act to decrease overall pathogenicity resulting in longer lifespans of the host to permit maximized transmission to new hosts. In this talk I will present the study of virulence factors from both Yersinia spp.and Salmonella spp.Starting with an exploration of their molecular structures, I will demonstrate their mechanism of action from the biochemical to the cellular level, and correlate this activity directly to virulence.  This will be followed by data on a newly discovered antivirulence pathway that is conserved in Salmonella spp.The combination of structural biology and proteomics based approacheshas permitted the construction of a molecular model of this membrane multi-protein complex.  Finally, I will discuss a unique secretion mechanism that appears to be common toE. coli, Yersinia spp., Salmonella spp., and related bacteria, and point out the potential of this system for biotechnological applications. The take-home message of this seminar is to underscore the diverse mechanisms used by bacteria to control their proliferation within a host.