YraP Contributes to Cell Envelope Integrity and Virulence of Salmonella enterica Serovar Typhimurium

Mutations in σ -regulated lipoproteins have previously been shown to impact bacterial viability under conditions of stress and during infection. YraP is conserved across a number of Gram-negative pathogens, including , where the homolog is a component of the Bexsero meningococcal group B vaccine. Investigations using laboratory-adapted K-12 have shown that mutants have elevated sensitivity to a range of compounds, including detergents and normally ineffective antibiotics. In this study, we investigate the role of the outer membrane lipoprotein YraP in the pathogenesis of serovar Typhimurium. We show that mutations in Typhimurium result in a defective outer membrane barrier with elevated sensitivity to a range of compounds. This defect is associated with attenuated virulence in an oral infection model and during the early stages of systemic infection. We show that this attenuation is not a result of defects in lipopolysaccharide and O-antigen synthesis, changes in outer membrane protein levels, or the ability to adhere to and invade eukaryotic cell lines .