Figure 1. PhoPQ-regulated remodeling of outer membrane structures.
(A) Structural organization of the S. Typhimurium outer membrane (OM). PagP hydrolyzes palmitoyl groups of carbon length sixteen (C16:0) from glycerophospholipid (GPL) donor substrates and transfers them to lipid A molecules with six acyl substituents of carbon length twelve (C12:0) and fourteen (C14:0), or to the polar head group of phosphatidylglycerol (PG) molecules that have flipped (dashed arrow) into the OM outer leaflet on account of PhoPQ activation, or OM damage inflicted by antimicrobial peptides. The PagP palmitoyltransferase produces lipid A molecules with seven acyl chains with one palmitoyl group, as well as triacylated palmitoyl-PG molecules with a palmitoyl group extending from the sn-3’ head-group position [35]. (B) PhoPQ regulates the chemical structure of S. Typhimurium lipopolysaccharides (LPS). Modifications in red are directly regulated by the PhoPQ system. Those in blue are indirectly regulated by the PhoPQ system through the PmrA response regulator. Dashed lines indicate acyl groups cleaved by PagL and PagP. (C) Chemical structures of specific S. Typhimurium GPL. The PagP enzyme transfers palmitoyl groups from the sn-1 position of GPL donor substrates to the sn-3’ position of PG acceptor substrates by transesterification. The two palmitoyl-PG species depicted are generated by the PagP enzyme within the OM of S. Typhimurium [35]. CL = cardiolipin, or diphosphatidylglycerol, PE = phosphatidylethanolamine, acyl-PG = acylphosphatidyglycerols.