Lipopolysaccharide inner core oligosaccharide structure and outer membrane stability in human pathogens belonging to the Enterobacteriaceae

Abstract

In the Enterobacteriaceae, the outer membrane is primarily comprised of lipopolysaccharides. The lipopolysaccharide molecule is important in mediating interactions between the bacterium and its environment and those regions of the molecule extending further away from the cell surface show a higher amount of structural diversity. The hydrophobic lipid A is highly conserved, due to its important role in the structural integrity of the outer membrane. Attached to the lipid A region is the core oligosaccharide. The inner core oligosaccharide (lipid A proximal) backbone is also well conserved. However, non-stoichiometric substitutions of the basic inner core structure lead to structural variation and microheterogeneity. These include the addition of negatively charged groups (phosphate or galacturonic acid), ethanolamine derivatives, and glycose residues (Kdo, rhamnose, galactose, glucosamine, N-acetylglucosamine, heptose, Ko). The genetics and biosynthesis of these substitutions is beginning to be elucidated. Modification of heptose residues with negatively charged molecules (such as phosphate in Escherichia coli and Salmonella and galacturonic acid in Klebsiella pneumoniae) has been shown to be involved in maintaining membrane stability. However, the biological role(s) of the remaining substitutions is unknown.

Structure of Compositionally Simple Lipopolysaccharide from Marine Synechococcus

“…LPS has been observed. This occurs in environmental isolates, and this modification has been thought to give the bacteria an advantage in low-phosphate conditions (5). Similarly, galacturonic acid can replace the 4Ј phosphate of Rhizobium sp.…”

Down-Regulation of Key Virulence Factors Makes the Salmonella enterica Serovar Typhimurium rfaH Mutant a Promising Live-Attenuated Vaccine Candidate

“…Due to decreased LPS synthesis, the bacterial demand for sugars is much reduced, which could account for the downregulation of sugar transporters. Moreover, the (deep-)rough phenotype has a huge impact on the stability of the bacterial envelope (19), rearrangement of which can be considered a clear compensatory change. Interestingly, virK and mig-14 have been shown to be involved in resistance to antimicrobial pep-tides (7).…”

Absence of PmrAB-Mediated Phosphoethanolamine Modifications of Citrobacter rodentium Lipopolysaccharide Affects Outer Membrane Integrity

“…Among the other LPS-modifying PmrA-regulated genes, C. rodentium possesses the pmrC and cptA homologues. The pmrC and cptA genes encode pEtN transferases responsible for mediating the addition of pEtN to the 1 and 4Ј phosphates of lipid A and to the phosphate of heptose I found in the LPS core, respectively (12,29). Addition of pEtN to lipid A or the LPS core has been shown to have a modest effect on PMB resistance (13,14,34).…”

“…LPS modifications decrease OM permeability by adding palmitate to lipid A (encoded by the pagP gene) (29). They also neutralize negative charges of LPS by adding 4-aminoarabinose (encoded by the arn operon) or phosphoethanolamine (pEtN) (encoded by the pmrC and cptA genes) to specific phosphate groups (12,29). Early studies have highlighted an association between PmrABmediated modifications of LPS and increased resistance of Salmonella enterica to the AMP polymyxin B (PMB) (36,37).…”