The structure of the O‐specific chain of <i>Legionella pneumophila</i> serogroup 1 lipopolysaccharide

Knirel, Yuriy A.; Rietschel, Ernst; Marre, R.; Zähringer, Ulrich

doi:10.1111/j.1432-1033.1994.tb18734.x

Cited by 119 publications

(110 citation statements)

References 39 publications

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“…4A), have been called "Sia-like" molecules (41) and are found in over a dozen bacterial species including L. pneumophila, P. aeruginosa, and pathogenic Vibrio spp (42). Biochemical analysis has shown that Leg and Pse molecules on the surfaces of L. pneumophila, P. aeruginosa, and C. jejuni are modified by O-acetylation (12,14,16). We now show that like the Neu5Ac biosynthetic clusters, both Leg and Pse biosynthetic clusters also include a neuD homolog (Fig.…”

Section: Discussionmentioning

confidence: 79%

The Group B Streptococcal Sialic Acid O-Acetyltransferase Is Encoded by neuD, a Conserved Component of Bacterial Sialic Acid Biosynthetic Gene Clusters

Lewis

Hensler

Varki

et al. 2006

Journal of Biological Chemistry

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Nearly two dozen microbial pathogens have surface polysaccharides or lipo-oligosaccharides that contain sialic acid (Sia), and several Sia-dependent virulence mechanisms are known to enhance bacterial survival or result in host tissue injury. Some pathogens are also known to O-acetylate their Sias, although the role of this modification in pathogenesis remains unclear. We report that neuD, a gene located within the Group B Streptococcus (GBS) Sia biosynthetic gene cluster, encodes a Sia O-acetyltransferase that is itself required for capsular polysaccharide (CPS) sialylation. Homology modeling and site-directed mutagenesis identified Lys-123 as a critical residue for Sia O-acetyltransferase activity. Moreover, a single nucleotide polymorphism in neuD can determine whether GBS displays a "high" or "low" Sia O-acetylation phenotype. Complementation analysis revealed that Escherichia coli K1 NeuD also functions as a Sia O-acetyltransferase in GBS. In fact, NeuD homologs are commonly found within Sia biosynthetic gene clusters. A bioinformatic approach identified 18 bacterial species with a Sia biosynthetic gene cluster that included neuD. Included in this list are the sialylated human pathogens Legionella pneumophila, Vibrio parahemeolyticus, Pseudomonas aeruginosa, and Campylobacter jejuni, as well as an additional 12 bacterial species never before analyzed for Sia expression. Phylogenetic analysis shows that NeuD homologs of sialylated pathogens share a common evolutionary lineage distinct from the poly-Sia O-acetyltransferase of E. coli K1. These studies define a molecular genetic approach for the selective elimination of GBS Sia O-acetylation without concurrent loss of sialylation, a key to further studies addressing the role(s) of this modification in bacterial virulence.Sialic acids (Sias) 3 are a family of related nine-carbon acidic sugars (nonulosonic acids) that are found at the outer ends of glycan chains on all vertebrate cells. Over 20 microbial pathogens are known to use surface Sia decoration as a form of molecular mimicry that is often crucial to virulence (1). Several convergent strategies for microbial Sia decoration have been identified, including endogenous biosynthesis, scavenging, or direct transfer of host Sias to their own surface glycans (1). Heavily sialylated bacteria often cause sepsis and meningitis by exhibiting Sia-dependent serum resistance due to deactivation of the alternative complement pathway (2-4). In addition, bacterial Sias can enhance intracellular survival (5), participate in biofilm formation (6), or mask underlying antibody epitopes (7). Antibodies elicited against sialylated bacterial glycolipids can also cross-react with host peripheral nerve axons, leading to the debilitating autoimmune disorder called GuillainBarré syndrome (8, 9). In short, there are multiple Sia-dependent virulence mechanisms that enhance bacterial survival and/or result in host tissue injury.Several pathogenic bacteria are known to modify Sia residues by O-acetylation (10 -18). In other contexts, ...

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Section: Discussionmentioning

confidence: 79%

The Group B Streptococcal Sialic Acid O-Acetyltransferase Is Encoded by neuD, a Conserved Component of Bacterial Sialic Acid Biosynthetic Gene Clusters

Lewis

Hensler

Varki

et al. 2006

Journal of Biological Chemistry

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“…Recently, the structure of the 0-specific chain of LPS of L. pneumophila serogroup 1 strain Philadelphia 1 was elucidated [16]. In order to identify LPS-associated epitopes, a panel of 10 MAbs was employed in the present study.…”

Section: J H Helbig and Othersmentioning

confidence: 99%

Molecular characterization of a virulence-associated epitope on the lipopolysaccharide ofLegionella pneumophilaserogroup 1

et al. 1995

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SUMMARYFor identification of lipopolysaccharide (LPS)-associated epitopes of Legionella pneumophila serogroup 1, LPS of strain Philadelphia 1 was investigated using monoclonal antibodies (MAbs). The 0-specific chain of LPS is a homopolymer of 5-acetamidino-7-acetamido-8-0-acetyl-3,5,7,9-tetradeoxy-D-glycero-L-galactononulosonic acid. At least four immunoaccessible epitopes were recognized by different MAbs on the intact LPS. After O-deacetylation of LPS, the reactivity of one of the MAbs (MAb 3/1) was lost, indicating thus that the corresponding epitope is associated with the 8-0-acetyl group. Since the reactivity pattern of the MAb 3/1 is identical with those of the MAb 2 which was considered as a virulence marker for serogroup 1, this epitope may be involved in mediating virulence in L. pneumophila. Four MAbs specific to strains of serogroup 1 other than the monoclonal subtype Philadelphia recognized epitopes on the O-deacetylated LPS of strain Philadelphia 1 and, therefore, the virulence-associated epitope blocks recognition of the immunodeterminants that are accessible on the intact LPS of the strains lacking this epitope.

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“…That allows to do sero-and subtyping of Legionella as demonstrated previously [21]. The O-chain of Legionella LPS consists of a homopolymer of legionaminic acid [26] that exhibits distinct acetylation patterns. These are expected to mediate serologic specificity and antibody binding [28].…”

Section: Discussionmentioning

confidence: 98%

Human Anti-Lipopolysaccharid (LPS) antibodies against Legionella with high species specificity

Kühn

Thiem

Steinert

et al. 2019

HAB

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Abstract. Legionella are Gram-negative bacteria that are ubiquitously present in natural and man-made water reservoirs. When humans inhale aerosolized water contaminated with Legionella, alveolar macrophages can be infected, which may lead to a lifethreatening pneumonia called Legionnaires' disease. Due to the universal distribution of Legionella in water and their potential threat to human health, the Legionella concentration in water for human use must be strictly monitored, which is difficult since the standard detection still relies on lengthy cultivation and analysis of bacterial morphology. In this study, an antibody against L. pneumophila has been generated from the naïve human HAL antibody libraries by phage-display for the first time. The panning was performed on whole bacterial cells in order to select antibodies that bind specifically to the cell surface of untreated Legionella. The bacterial cell wall component lipopolysaccharide (LPS) was identified as the target structure. Specific binding to the important pathogenic L. pneumophila strains Corby, Philadelphia-1 and Knoxville was observed, while no binding was detected to seven members of the families Enterobacteriaceae, Pseudomonadaceae or Clostridiaceae. Production of this antibody in the recombinant scFv-Fc format using either a murine or a human Fc part allowed the set-up of a sandwich-ELISA for detection of Legionella cells. The scFv-Fc construct proved to be very stable, even when stored for several weeks at elevated temperatures. A sensitivity limit of 4,000 cells was achieved. The scFv-Fc antibody pair was integrated on a biosensor, demonstrating the specific and fast detection of L. pneumophila on a portable device. With this system, 10,000 Legionella cells were detected within 35 min. Combined with a water filtration/concentration system, this antibody may be developed into a promising reagent for rapid on-site Legionella monitoring.

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The structure of the O‐specific chain of Legionella pneumophila serogroup 1 lipopolysaccharide

Cited by 119 publications

References 39 publications

The Group B Streptococcal Sialic Acid O-Acetyltransferase Is Encoded by neuD, a Conserved Component of Bacterial Sialic Acid Biosynthetic Gene Clusters

The Group B Streptococcal Sialic Acid O-Acetyltransferase Is Encoded by neuD, a Conserved Component of Bacterial Sialic Acid Biosynthetic Gene Clusters

Molecular characterization of a virulence-associated epitope on the lipopolysaccharide ofLegionella pneumophilaserogroup 1

Human Anti-Lipopolysaccharid (LPS) antibodies against Legionella with high species specificity

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