Regulation of Lipid A Modifications by <i>Salmonella typhimurium</i> Virulence Genes <i>phoP-phoQ</i>

TLDR

Bacterial pathogenesis depends on proteins that sense host microenvironments and regulate virulence gene transcription. In Salmonella, the PhoP‑PhoQ two‑component system regulates genes essential for intracellular survival and resistance to cationic peptides. PhoP‑PhoQ controls lipid A modifications—adding aminoarabinose and 2‑hydroxymyristate—that alter LPS‑induced E‑selectin and TNF‑α expression, suggesting these structural changes help Salmonella gain a host advantage.

Abstract

Bacterial pathogenesis requires proteins that sense host microenvironments and respond by regulating virulence gene transcription. For Salmonellae, one such regulatory system is PhoP-PhoQ, which regulates genes required for intracellular survival and resistance to cationic peptides. Analysis by mass spectrometry revealed that Salmonella typhimurium PhoP-PhoQ regulated structural modifications of lipid A, the host signaling portion of lipopolysaccharide (LPS), by the addition of aminoarabinose and 2-hydroxymyristate. Structurally modified lipid A altered LPS-mediated expression of the adhesion molecule E-selectin by endothelial cells and tumor necrosis factor–α expression by adherent monocytes. Thus, altered responses to environmentally induced lipid A structural modifications may represent a mechanism for bacteria to gain advantage within host tissues.