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 the host immunity barrier. The aim of this study was to define the role and interaction of PmrAB-dependent gene products required for the lipopolysaccharide component synthesis or modification mainly during the Salmonella infection. The PmrAB two-component system activation promotes a remodeling of lipid A and the 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 wzz(fepE) and wzz(st) genes is induced, and their products are required to determine the O-antigen chain length. Here we report for the first time that Wzz(st) 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 pbgE(2) and pbgE(3) 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.
Highlights
Introduction of Gene Mutations in theSalmonella Chromosome and Plasmid Construction—The one-step gene inactivation method [34] was used to generate deletion of the pbgE2 or pbgE3 complete coding sequence
We demonstrated that when RcsB is activated the Wzzst protein is involved in the negative control of flagella in hyperflagellated bacteria [24]
The wzzst Gene Product Is Involved in Lipid A Modification in a PmrAB-dependent Manner—In a previous work, we reported that expression of wzzst is controlled by two regulatory systems, PmrAB and RcsCDB
Summary
Introduction of Gene Mutations in theSalmonella Chromosome and Plasmid Construction—The one-step gene inactivation method [34] was used to generate deletion of the pbgE2 or pbgE3 complete coding sequence. Conclusion: PmrAB system is the master regulator of LPS remodeling, modulating genes that modify lipid A, core, and O-antigen. The aim of this study was to define the role and interaction of PmrAB-dependent gene products required for the lipopolysaccharide component synthesis or modification mainly during the Salmonella infection. The PmrAB two-component system activation promotes a remodeling of lipid A and the core region by addition of 4-aminoarabinose and/or phosphoethanolamine. 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
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