The PmrAB-inducing conditions control both lipid A remodelling and O-antigen length distribution, influencing the Salmonella Typhimurium-host interactions

Abstract

The Salmonella enterica serovar Typhimurium lipopolysaccharide consisting of covalently linked lipid A, non-repeating core oligosaccharide and the O-antigen polysaccharide, is the most exposed component of the cell envelope. Previous studies demonstrated that all of these regions act against host immunity barrier. The aim of this study was to define the role and interaction of PmrAB-dependent gene products required for the lipopolysaccharide components synthesis or modification, mainly during the Salmonella infection. The PmrAB two-component system activation promotes a remodelling of lipid A and core region by addition of 4-aminoarabinose and/or phosphoethanolamine. These PmrA-dependent activities are produced by activation of ugd, pbgPE, pmrC, cpta and pmrG transcription. In addition, under PmrA regulator activation the expression of wzzfepE and wzzst genes are induced and their products are required to determine the O-antigen chain length. We here report for the first time that Wzzst protein is necessary to maintain the balance of 4-aminoarabinose and phosphoethanolamine-lipid A modifications. Moreover, we demonstrate that the interaction of the PmrA-dependent pbgE2 and pbgE3 gene products is important for the formation of the short O-antigen region. Our results establish that PmrAB is the global regulatory system that controls lipopolysaccharide modification, leading to a coordinate regulation of 4-aminoarabinose incorporation and O-antigen chain length to respond against the host defense mechanisms.