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Review
. 2014 Feb:17:106-13.
doi: 10.1016/j.mib.2013.12.005. Epub 2014 Feb 14.

Salmonellae PhoPQ regulation of the outer membrane to resist innate immunity

Zachary D Dalebroux  1 , Samuel I Miller  2
Affiliations
Review

Salmonellae PhoPQ regulation of the outer membrane to resist innate immunity

Zachary D Dalebroux et al. Curr Opin Microbiol. 2014 Feb.

Abstract

Salmonellae sense host cues to regulate properties important for bacterial survival and replication within host tissues. The PhoPQ two-component regulatory system senses phagosome acidification and cationic antimicrobial peptides (CAMP) to regulate the protein and lipid contents of the bacterial envelope that comprises an inner and outer membrane. PhoPQ-regulated lipid components of the outer membrane include lipopolysaccharides and glycerophospholipids. Envelope proteins regulated by PhoPQ, include: components of virulence associated secretion systems, the flagellar apparatus, membrane transport systems, and proteins that are likely structural components of the outer membrane. PhoPQ alteration of the bacterial surface results in increased bacterial resistance to CAMP and decreased detection by the innate immune system. This review details the molecular complexity of the bacterial cell envelope and highlights the outer membrane lipid bilayer as an environmentally regulated bacterial organelle.

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Figures

Figure 1
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.
Figure 2
Figure 2. Bacterial adaptation to host antimicrobial peptides requires coordinated synthesis of diverse OM structures
Cationic antimicrobial peptides (CAMP) like C18G, an amphipathic alpha-helical human-derived cathelicidin, damage acute outer membrane (OM) surfaces to expose a thin layer of peptidoglycan, the periplasmic space, and eventually the inner membrane (IM). PhoQ binds CAMP on the outer leaflet of the IM to activate phosphorylation of PhoP, which induces PmrA and its regulon. PmrA regulates: ArnT, an aminoarabinose (L-Ara4N) transferase, EptA, a lipid A phosphoethanolamine (pEtN) transferase, Wzzst, a long-type O-antigen translocase, and CptA, a LPS core pEtN transferase.
See this image and copyright information in PMC

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