Explore the vast range of titles available.

In plants, cell-surface immune receptors sense molecular non–self-signatures. Lipid A of Gram-negative bacterial lipopolysaccharide is considered such a non–self-signature. The receptor kinase LIPOOLIGOSACCHARIDE-SPECIFIC REDUCED ELICITATION (LORE) mediates plant immune responses to Pseudomonas and Xanthomonas but not enterobacterial lipid A or lipopolysaccharide preparations. Here, we demonstrate that synthetic and bacterial lipopolysaccharide-copurified medium-chain 3-hydroxy fatty acid (mc-3-OH-FA) metabolites elicit LORE-dependent immunity.The mc-3-OH-FAs are sensed in a chain length– and hydroxylation-specific manner, with free (R)-3-hydroxydecanoic acid [(R)-3-OH-C10:0] representing the strongest immuneelicitor. By contrast, bacterial compounds comprising mc-3-OH-acyl building blocks but devoid of free mc-3-OH-FAs—including lipid A or lipopolysaccharide, rhamnolipids, lipopeptides, and acyl-homoserine-lactones—do not trigger LORE-dependent responses. Hence, plants sense low-complexity bacterial metabolites to trigger immune responses.

The outer membrane (OM) of the diderm gramnegative class of bacteria is an essential organelle and a robust permeability barrier that prevents many antibiotics from reaching their intracellular targets. The OM is a unique asymmetrical lipid bilayer: The inner leaflet is composed of phospholipids (PLs), and the outer leaflet consists almost exclusively of a glycolipid referred to either as lipopolysaccharide (LPS, in bacteria that attach long repeats of sugars to the glycolipid) or lipooligosaccharide (LOS, in bacteria that attach only a short oligosaccharide to cap the glycolipid). Even though it is used sparingly in last-resort treatments, colistin has not escaped the evolution of resistance. Typically, any of several enzymatic modifications of LPS/LOS can reduce its negative charge, and thereby decrease colistin binding. Acinetobacter baumannii is a common multidrug-resistant human pathogen that is clinically treated with colistin. Powers and Trent examine A. baumannii strains that have taken the remarkable step of inactivating LOS production entirely to become highly colistin resistant.

Axonal variants of Guillain–Barré syndrome (GBS) mainly include acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, and pharyngeal-cervical-brachial weakness. Molecular mimicry of human gangliosides by a pathogen's lipooligosaccharides is a well-established mechanism for Campylobacter jejuni-associated GBS. New triggers of the axonal variants of GBS (axonal GBS), such as Zika virus, hepatitis viruses, intravenous administration of ganglioside, vaccination, and surgery, are being identified. However, the pathogenetic mechanisms of axonal GBS related to antecedent bacterial or viral infections other than Campylobacter jejuni remain unknown. Currently, autoantibody classification and serial electrophysiology are cardinal approaches to differentiate axonal GBS from the prototype of GBS, acute inflammatory demyelinating polyneuropathy. Newly developed technologies, including metabolite analysis, peripheral nerve ultrasound, and feature selection via artificial intelligence are facilitating more accurate diagnosis of axonal GBS. Nevertheless, some key issues, such as genetic susceptibilities, remain unanswered and moreover, current therapies bear limitations. Although several therapies have shown considerable benefits to experimental animals, randomized controlled trials are still needed to validate their efficacy.

Acinetobacter baumannii is a multidrug-resistant pathogen that produces lipooligosaccharide (LOS), a glycolipid that confers protective asymmetry to the bacterial outer membrane. The core oligosaccharide is a ubiquitous component of LOS that typically follows a well-established model of synthesis. In addition to providing an extensive analysis of the genes involved in the synthesis of the core region, we demonstrate that this organism has evidently diverged from the long-held archetype of core synthesis. Moreover, our data suggest that A. baumannii LOS assembly is important for cell division and likely intersects with the synthesis of the peptidoglycan cell wall, another essential component of the Gram-negative cell envelope. This connection between LOS and cell wall synthesis provides an intriguing foundation for a unique method of outer membrane biogenesis and cell envelope coordination.

The cell-envelope of Gram-negative bacteria contains endotoxic lipopolysaccharides (LPS) that are recognized by the innate immune system via Toll-Like Receptors (TLRs). The intestinal mucosal symbiont Akkermansia muciniphila is known to confer beneficial effects on the host and has a Gram-negative architecture. Here we show that A. muciniphila LPS lacks the O-polysaccharide repeating unit, with the resulting lipooligosaccharide (LOS) having unprecedented structural and signaling properties. The LOS consists of a complex glycan chain bearing two distinct undeca- and hexadecasaccharide units each containing three 2-keto-3-deoxy-D- manno -octulosonic acid (Kdo) residues. The lipid A moiety appears as a mixture of differently phosphorylated and acylated species and carries either linear or branched acyl moieties. Peritoneal injection of the LOS in mice increased higher gene expression of liver TLR2 than TLR4 (100-fold) and induced high IL-10 gene expression. A. muciniphila LOS was found to signal both through TLR4 and TLR2, whereas lipid A only induced TLR2 in a human cell line. We propose that the unique structure of the A. muciniphila LOS allows interaction with TLR2, thus generating an anti-inflammatory response as to compensate for the canonical inflammatory signaling associated with LOS and TLR4, rationalizing its beneficial host interaction. Here, the authors characterize the structure of the Lipooligosaccharide of the gut symbiont Akkermansia muciniphila showing unique features and TLR4 and TLR2 signaling capacity, which underscore the beneficial properties of this bacterium.

Outer membrane vesicles (OMVs) of in the group B-directed vaccine MenB-4C (Bexsero ) protect against infections with . The immunological basis for protection remains unclear. OMV vaccines generate human antibodies to and lipooligosaccharide (LOS/endotoxin), but the structural specificity of these LOS antibodies is not defined. Ten paired human sera obtained pre- and post-MenB-4C immunization were used in Western blots to probe and LOS. Post-MenB-4C sera (7v5, 19v5, and 17v5), representing individual human variability in LOS recognition, were then used to interrogate structurally defined LOSs of and strains and mutants and studied in bactericidal assays. Post-MenB-4C sera recognized both and LOS species, ~10% of total IgG to gonococcal OMV antigens. and LOSs were broadly recognized by post-IgG antibodies, but with individual variability for LOS structures. Deep truncation of LOS, specifically a K mutant without -, -, or -chain glycosylation, eliminated LOS recognition by all post-vaccine sera. Serum 7v5 IgG antibodies recognized the unsialyated L1 -chain, and a 3-PEA-HepII or 6-PEA-HepII was part of the conformational epitope. Replacing the 3-PEA on HepII with a 3-Glc blocked 7v5 IgG antibody recognition of and LOSs. Serum 19v5 recognized lactoneotetrose (LNT) or L1 LOS-expressing or with a minimal -chain structure of Gal-Glc-HepI (L8), a 3-PEA-HepII or 6-PEA-HepII was again part of the conformational epitope and a 3-Glc-HepII blocked 19v5 antibody binding. Serum 17v5 LOS antibodies recognized LNT or L1 -chains with a minimal HepI structure of three sugars and no requirement for HepII modifications. These LOS antibodies contributed to the serum bactericidal activity against . The MenB-4C vaccination elicits bactericidal IgG antibodies to conformational epitopes involving HepI and HepII glycosylated LOS structures shared between and LOS structures should be considered in next-generation gonococcal vaccine design.

Abstract Glycosylation of proteins is one of the most prevalent post-translational modifications occurring in nature, with a wide repertoire of biological implications. Pathways for the main types of this modification, the N- and O-glycosylation, can be found in all three domains of life—the Eukarya, Bacteria and Archaea—thereby following common principles, which are valid also for lipopolysaccharides, lipooligosaccharides and glycopolymers. Thus, studies on any glycoconjugate can unravel novel facets of the still incompletely understood fundamentals of protein N- and O-glycosylation. While it is estimated that more than two-thirds of all eukaryotic proteins would be glycosylated, no such estimate is available for prokaryotic glycoproteins, whose understanding is lagging behind, mainly due to the enormous variability of their glycan structures and variations in the underlying glycosylation processes. Combining glycan structural information with bioinformatic, genetic, biochemical and enzymatic data has opened up an avenue for in-depth analyses of glycosylation processes as a basis for glycoengineering endeavours. Here, the common themes of glycosylation are conceptualised for the major classes of prokaryotic (i.e. bacterial and archaeal) glycoconjugates, with a special focus on glycosylated cell-surface proteins. We describe the current knowledge of biosynthesis and importance of these glycoconjugates in selected pathogenic and beneficial microbes. The authors summarise current knowledge of prokaryotic glycobiology, focusing on structures and molecular details of biosynthesis concepts of glycoproteins and secondary cell-wall polymers, including their roles in prokaryotic life and their impact on pathogenicity as well as emerging glycoengineering strategies.

Campylobacter jejuni, causing strong enteritis, is an unusual bacterium with numerous peculiarities. Chemotactically controlled motility in viscous milieu allows targeted navigation to intestinal mucus and colonization. By phase variation, quorum sensing, extensive O-and N-glycosylation and use of the flagellum as type-3-secretion system C. jejuni adapts effectively to environmental conditions. C. jejuni utilizes proteases to open cell–cell junctions and subsequently transmigrates paracellularly. Fibronectin at the basolateral side of polarized epithelial cells serves as binding site for adhesins CadF and FlpA, leading to intracellular signaling, which again triggers membrane ruffling and reduced host cell migration by focal adhesion. Cell contacts of C. jejuni results in its secretion of invasion antigens, which induce membrane ruffling by paxillin-independent pathway. In addition to fibronectin-binding proteins, other adhesins with other target structures and lectins and their corresponding sugar structures are involved in host–pathogen interaction. Invasion into the intestinal epithelial cell depends on host cell structures. Fibronectin, clathrin, and dynein influence cytoskeletal restructuring, endocytosis, and vesicular transport, through different mechanisms. C. jejuni can persist over a 72-h period in the cell. Campylobacter-containing vacuoles, avoid fusion with lysosomes and enter the perinuclear space via dynein, inducing signaling pathways. Secretion of cytolethal distending toxin directs the cell into programmed cell death, including the pyroptotic release of proinflammatory substances from the destroyed cell compartments. The immune system reacts with an inflammatory cascade by participation of numerous immune cells. The development of autoantibodies, directed not only against lipooligosaccharides, but also against endogenous gangliosides, triggers autoimmune diseases. Lesions of the epithelium result in loss of electrolytes, water, and blood, leading to diarrhea, which flushes out mucus containing C. jejuni. Together with the response of the immune system, this limits infection time. Based on the structural interactions between host cell and bacterium, the numerous virulence mechanisms, signaling, and effects that characterize the infection process of C. jejuni, a wide variety of targets for attenuation of the pathogen can be characterized. The review summarizes strategies of C. jejuni for host–pathogen interaction and should stimulate innovative research towards improved definition of targets for future drug development.Key points• Bacterial adhesion of Campylobacter to host cells and invasion into host cells are strictly coordinated processes, which can serve as targets to prevent infection.• Reaction and signalling of host cell depend on the cell type.• Campylobacter virulence factors can be used as targets for development of antivirulence drug compounds.

The outer membrane of Gram-negative bacteria is a critical barrier that prevents entry of noxious compounds. Integral to this functionality is the presence of lipopolysaccharide (LPS) or lipooligosaccharide (LOS), a molecule that is located exclusively in the outer leaflet of the outer membrane. Its lipid anchor, lipid A, is a glycolipid whose hydrophobicity and net negative charge are primarily responsible for the robustness of the membrane. Because of this, lipid A is a hallmark of Gram-negative physiology and is generally essential for survival. Rare exceptions have been described, including Acinetobacter baumannii, which can survive in the absence of lipid A, albeit with significant growth and membrane permeability defects. Here, we show by an evolution experiment that LOS-deficient A. baumannii can rapidly improve fitness over the course of only 120 generations. We identified two factors which negatively contribute to fitness in the absence of LOS, Mla and PldA. These proteins are involved in glycerophospholipid transport (Mla) and lipid degradation (PldA); both are active only on mislocalized, surface-exposed glycerophospholipids. Elimination of these two mechanisms was sufficient to cause a drastic fitness improvement in LOS-deficient A. baumannii. The LOS-deficient double mutant grows as robustly as LOS-positive wild-type bacteriawhile remaining resistant to the last-resort polymyxin antibiotics. These data provide strong biological evidence for the directionality of Mla-mediated glycerophospholipid transport in Gram-negative bacteria and furthers our knowledge of asymmetry-maintenance mechanisms in the context of the outer membrane barrier.

Acinetobacter baumannii is a Gram-negative opportunistic zoonotic pathogenic bacterium that causes nosocomial infections ranging from minor to life-threatening. The clinical importance of this zoonotic pathogen is rapidly increasing due to the development of multiple resistance mechanisms and the synthesis of numerous virulence factors. Although no flagellum-mediated motility exists, it may move through twitching or surface-associated motility. Twitching motility is a coordinated multicellular movement caused by the extension, attachment, and retraction of type IV pili, which are involved in surface adherence and biofilm formation. Surface-associated motility is a kind of movement that does not need appendages and is most likely driven by the release of extra polymeric molecules. This kind of motility is linked to the production of 1,3-diaminopropane, lipooligosaccharide formation, natural competence, and efflux pump proteins. Since A. baumannii ’s virulence qualities are directly tied to motility, it is possible that its motility may be used as a specialized preventative or therapeutic measure. The current review detailed the signaling mechanism and involvement of various proteins in controlling A. baumannii motility. As a result, we have thoroughly addressed the role of natural and synthetic compounds that impede A. baumannii motility, as well as the underlying action mechanisms. Understanding the regulatory mechanisms behind A. baumannii ’s motility features will aid in the development of therapeutic drugs to control its infection. Key points • Acinetobacter baumannii exhibits multiple resistance mechanisms. • A. baumannii can move owing to twitching and surface-associated motility. • Natural and synthetic compounds can attenuate A. baumannii motility.