Remodelling of the Gram-negative bacterial Kdo2-lipid A and its functional implications

Abstract

The lipopolysaccharide (LPS) is a characteristic molecule of the outer leaflet of the Gram-negative bacterial outer membrane, which consists of lipid A, core oligosaccharide, and O antigen. The lipid A is embedded in outer membrane and provides an efficient permeability barrier, which is particularly important to reduce the permeability of antibiotics, toxic cationic metals, and antimicrobial peptides. LPS, an important modulator of innate immune responses ranging from localized inflammation to disseminated sepsis, displays a high level of structural and functional heterogeneity, which arise due to regulated differences in the acylation of the lipid A and the incorporation of non-stoichiometric modifications in lipid A and the core oligosaccharide. This review focuses on the current mechanistic understanding of the synthesis and assembly of the lipid A molecule and its most salient non-stoichiometric modifications.

Transposon sequencing reveals the essential gene set and genes enabling gut symbiosis in the insect symbiont Caballeronia insecticola

“…This gene cluster was in an independent approach found to be essential for viability in B. cenocepacia strain K56-2 [ 41 ]. The Ara4N modification of LPS mediates resistance against cationic antimicrobial peptides (AMPs) in many gram-negative bacteria, including Burkholderia species [ 42 ]. In the γ-proteobacteria Salmonella and Pseudomonas , the Ara4N modification is not essential and not constitutively present in lipid A but is introduced upon sensing of AMPs in the environment [ 43 - 46 ].…”

Transposon sequencing reveals the essential gene set and genes enabling gut symbiosis in the insect symbiontCaballeronia insecticola

“…This gene cluster was in an independent approach found to be essential for viability in B. cenocepacia strain K56-2 [41]. The Ara4N modification of LPS is a mechanism that mediates resistance against cationic antimicrobial peptides (AMPs) in many Gram-negative bacteria, including Burkholderia species [42]. In the γ-proteobacteria Salmonella and Pseudomonas , the Ara4N modification is not essential and not constitutively present in lipid A but is introduced upon sensing of AMPs in the environment [43–46].…”

Hundreds of antimicrobial peptides create a selective barrier for insect gut symbionts

“…The wzm , rfbA , wbiF , wbiG and wbiI mutants produced a similar LPS that lacked the O-antigen but had a lipid A/core oligosaccharide moiety that was indistinguishable from WT while the waaC and waaF mutants had an altered lipid A/core moiety, in agreement with the predicted heptosyl-transferase activity of the encoded enzymes that perform the first steps of the core oligosaccharide synthesis. Mass spectrometry analysis of the lipid A moieties suggested that none of the mutants had an altered lipid A structure and notably, that all mutants produced lipid A carrying the 4-amino-4-deoxy-L arabinose (Ara4N) modification that is known to confer PMB resistance in related species (34, 35, 39)(Fig. 4B; SI Appendix, Fig.…”