Lipopolysaccharide (LPS) is a component of the outer membrane of almost all Gram-negative bacteria and consists of lipid A, core sugars, and O-antigen. LPS is recognized by Toll-like receptor 4 (TLR4) and MD-2 on host innate immune cells and can signal to activate the transcription factor NFκB, leading to the production of pro-inflammatory cytokines that initiate and shape the adaptive immune r...

MsbA is an essential ATP-binding cassette half-transporter in the cytoplasmic membrane of the gram-negative Escherichia coli and is required for the export of lipopolysaccharides (LPS) to the outer membrane, most likely by transporting the lipid A core moiety. Consistent with the homology of MsbA to the multidrug transporter LmrA in the gram-positive Lactococcus lactis, our recent work in E. co...

Lipopolysaccharide (LPS) is a major constituent of bacterial outer membranes where it makes up the bulk of the outer leaflet and plays a key role as determinant of bacterial interactions with the host. Membrane-free LPS is known to activate T-lymphocytes through interactions with Toll-like receptor 4 via multiprotein complexes. In the present study, we investigate the role of cholesterol and me...

Pseudomonas cepacia was found to be resistant to the outer membrane-permeabilizing effects of aminoglycoside antibiotics, polymyxin B, and EDTA. Permeabilization of P. cepacia to the fluorescent probe 1-N-phenylnaphthylamine was not achieved at concentrations 100- to 1,000-fold above those required to permeabilize Pseudomonas aeruginosa. Furthermore, in contrast to P. aeruginosa cells, intact c...

Antibodies to Escherichia coli J5, a uridine 5'-diphosphate-galactose epimerase-less mutant of E. coli 0111, neutralized meningococcal endotoxemia from all three major capsular serogroups. We chose the dermal necrosis of the local Shwartzman phenomenon and the renal cortical necrosis of the general Shwartzman phenomenon as assays because these are the hallmarks of meningococcemia, and because m...

BACKGROUND Lipopolysaccharide (LPS), a lipoglycan from the outer membrane of Gram-negative bacteria, is an immunomodulatory molecule that stimulates the innate immune response. High levels of LPS cause excessive release of inflammatory mediators and are responsible for the septic shock syndrome. The interaction of LPS with its cognate binding proteins has not, as yet, been structurally elucidat...

Many pathogens are equipped with factors providing resistance against the bactericidal action of complement. Yersinia enterocolitica, a Gram-negative enteric pathogen with invasive properties, efficiently resists the deleterious action of human complement. The major Y. enterocolitica serum resistance determinants include outer membrane proteins YadA and Ail. Lipopolysaccharide (LPS) O-antigen (...

Lipopolysaccharide (LPS) is an essential component of the outer membrane (OM) in most gram-negative bacteria, and its structure and biosynthetic pathway are well known. Nevertheless, the mechanisms of transport and assembly of this molecule at the cell surface are poorly understood. The inner membrane (IM) transport protein MsbA is responsible for flipping LPS across the IM. Additional componen...

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. LPS elicits strong immunopathological responses during bacterial infection, and the lipid A moiety of LPS is responsible for this immunostimulatory activity. Lipid A exerts its biological activity by sending signals via TLR4 present on immune cells, and TLR4 agonists have been a target for vaccine adj...

The asymmetric outer membrane (OM) of Gram-negative bacteria contains lipopolysaccharide (LPS) in the outer leaflet and phospholipid in the inner leaflet. During OM biogenesis, LPS is transported from the periplasm into the outer leaflet by a complex comprising the OM proteins LptD and LptE. Recently, a new family of macrocyclic peptidomimetic antibiotics that interact with LptD of the opportun...