Gram negative bacteria possess a unique, selectively permeable outer membrane, comprised of an asymmetric bilayer, containing Lipopolysaccharides (LPS) on the outer leaflet and phospholipids on the inner leaflet. The structure of this membrane, limits entry to potentially toxic and noxious substances, including a number of antibiotics, in addition to enhancing the bacteria’s ability to survive stressful environments, including those encountered during in vivo infection.
In this study we have identified PlpA, a protein previously of unknown function. PlpA is a lipoprotein localised to the inner leaflet of the outer membrane and conserved across the gamma proteobacteria. We have determined the structure of PlpA from E. coli K12 using NMR. In this study we have shown PlpA is required for the correct formation and maintenance of the outer membrane barrier function, deletion in either the laboratory strain E. coli K12 or the human pathogen Salmonella enterica serovar Typhimurium results elevated sensitivity to a number of antibiotics and noxious compounds, including vancomycin and sodium dodecyl sulphate. We have generated suppressor mutants to counteract the negative effects of plpA mutation.
We have shown plpA mutants in S. enterica serovar Typhimurium are highly attenuated in the mouse mode during early systemic infection. These data emphasise the need for further functional investigation of this protein, to determine its role in membrane maintenance and bacterial pathogenesis.