Lipooligosaccharide of Campylobacter jejuni

Houliston, R. Scott; Vinogradov, Evgeny; Dzieciątkowska, Monika; Li, Jianjun; Michael, Frank St.; Karwaski, Marie-France; Brochu, Denis; Jarrell, Harold C.; Parker, Craig T.; Yuki, Nobuhiro; Mandrell, Robert E.; Gilbert, Michel

doi:10.1074/jbc.m110.181750

Cited by 51 publications

(51 citation statements)

References 34 publications

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“…The genetic basis for the generation of antigenic variation in bacterial surface molecules has been extensively studied over the last decade [14], [15], [25]. Regulation of gene expression by phase variation is documented in Campylobacter spp.…”

Section: Discussionmentioning

confidence: 99%

Structural Heterogeneity of Terminal Glycans in Campylobacter jejuni Lipooligosaccharides

et al. 2012

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Lipooligosaccharides of the gastrointestinal pathogen Campylobacter jejuni are regarded as a major virulence factor and are implicated in the production of cross-reactive antibodies against host gangliosides, which leads to the development of autoimmune neuropathies such as Guillain-Barré and Fisher Syndromes. C. jejuni strains are known to produce diverse LOS structures encoded by more than 19 types of LOS biosynthesis clusters. This study demonstrates that the final C. jejuni LOS structure cannot always be predicted from the genetic composition of the LOS biosynthesis cluster, as determined by novel lectin array analysis of the terminal LOS glycans. The differences were shown to be partially facilitated by the differential on/off status of three genes wlaN , cst and cj1144-45. The on/off status of these genes was also analysed in C. jejuni strains grown in vitro and in vivo, isolated directly from the host animal without passaging, using immunoseparation. Importantly, C. jejuni strains 331, 421 and 520 encoding cluster type C were shown to produce different LOS, mimicking asialo GM 1 , asialo GM 2 and a heterogeneous mix of gangliosides and other glycoconjugates respectively. In addition, individual C. jejuni colonies were shown to consistently produce heterogeneous LOS structures, irrespective of the cluster type and the status of phase variable genes. Furthermore we describe C. jejuni strains (351 and 375) with LOS clusters that do not match any of the previously described LOS clusters, yet are able to produce LOS with asialo GM 2 -like mimicries. The LOS biosynthesis clusters of these strains are likely to contain genes that code for LOS biosynthesis machinery previously not identified, yet capable of synthesising LOS mimicking gangliosides.

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Section: Discussionmentioning

confidence: 99%

Structural Heterogeneity of Terminal Glycans in Campylobacter jejuni Lipooligosaccharides

et al. 2012

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“…In Campylobacter jejuni, the most common cause of bacterial gastroenteritis, CMP-Neu5Ac biosynthesis ( neuA, neuB, and neuC ) and GT-42 genes are present in the lipooligosaccharide (LOS) biosynthesis locus classes A, B, C, M, R, and V (8-10). C. jejuni strains carrying one of these genetic classes synthesize LOS structures generally resembling gangliosides (9, 11-13). In some cases, infection with a C. jejuni strain expressing ganglioside-like LOS induces production of cross-reactive anti-ganglioside antibodies.…”

Section: Introductionmentioning

confidence: 99%

Genetics behind the biosynthesis of nonulosonic acid containing lipooligosaccharides inCampylobacter coli

Culebro

Gilbert

Stupak³

et al. 2018

Preprint

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“…Host-like glycans are also expressed by lipooligosaccharides (LOSs) of N. gonorrhoeae, N. meningitidis, Campylobacter jejuni and H. influenzae (Aspinall, et al, 1994, Houliston, et al, 2011, Mandrell and Apicella, 1993, Mandrell, et al, 1988, Yuki, et al, 2004, Yuki, et al, 1993, Mandrell, 1992). Relevant to this review, two ‘host-like’ structures expressed by Neisserial LOS structures include lacto- N -neotetraose (LNnT; Galβ1-4GlcNAcβ1-3Galβ1-4Glc), identical to the terminal tetrasaccharide of paragloboside, a precursor of the major human blood group antigens (Mandrell, et al, 1988), and globotriose (Galα1-4Galβ1-4Glc) that is identical to terminal globotriose trisaccharide of the P K -like blood group antigen (Mandrell, 1992).…”

Section: Introductionmentioning

confidence: 99%

Utilizing complement evasion strategies to design complement-based antibacterial immunotherapeutics: Lessons from the pathogenic Neisseriae

et al. 2016

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Novel therapies are urgently needed to combat the global threat of multidrug-resistant pathogens. Complement forms an important arm of innate defenses against infections. In physiological conditions, complement activation is tightly controlled by soluble and membrane-associated complement inhibitors, but must be selectively activated on invading pathogens to facilitate microbial clearance. Many pathogens, including Neisseria gonorrhoeae and N. meningitidis, express glycans, including N-acetylneuraminic acid (Neu5Ac), that mimic host structures to evade host immunity. Neu5Ac is a negatively charged 9-cabon sugar that inhibits complement, in part by enhancing binding of the complement inhibitor factor H (FH) through C-terminal domains (19 and 20) on FH. Other microbes also bind FH, in most instances through FH domains 6 and 7 or 18-20. Here we describe two strategies to target complement activation on Neisseriae. First, microbial binding domains of FH were fused to IgG Fc to create FH18-20/Fc (binds gonococci) and FH6,7/Fc (binds meningococci). A point mutation in FH domain 19 eliminated hemolysis caused by unmodified FH18-20, but retained binding to gonococci. FH18-20/Fc and FH6,7/Fc mediated complement-dependent killing in vitro and showed efficacy in animal models of gonorrhea and meningococcal bacteremia, respectively. The second strategy utilized CMP-nonulosonate (CMP-NulO) analogs of sialic acid that were incorporated into LOS and prevented complement inhibition by physiologic CMP-Neu5Ac and resulted in attenuated gonococcal infection in mice. While studies to establish the safety of these agents are needed, enhancing complement activation on microbes may represent a promising strategy to treat antimicrobial resistant organisms.

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Lipooligosaccharide of Campylobacter jejuni

Cited by 51 publications

References 34 publications

Structural Heterogeneity of Terminal Glycans in Campylobacter jejuni Lipooligosaccharides

Structural Heterogeneity of Terminal Glycans in Campylobacter jejuni Lipooligosaccharides

Genetics behind the biosynthesis of nonulosonic acid containing lipooligosaccharides inCampylobacter coli

Utilizing complement evasion strategies to design complement-based antibacterial immunotherapeutics: Lessons from the pathogenic Neisseriae

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