Lipopolysaccharide Heterogeneity in the Atypical Group of Novel Emerging Brucella Species

Zygmunt, Michel S.; Jacques, Isabelle; Bernardet, Nelly; Cloeckaert, Axel

doi:10.1128/cvi.00300-12

Cited by 34 publications

(33 citation statements)

References 36 publications

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“…Furthermore, during the last decade, Brucella has been identified as a pathogen of several marine mammals, and MAb reactivity patterns almost identical to that described here for B. suis biovar 2 have been reported for B. ceti strains isolated from some dolphin species [28]. Also, like B. suis biovar 2, several Brucella strains isolated from wild rodents in Australia do not react with MAb of C and M specificities [29]. Thus, it seems that the A-positive, C and M-negative epitopic structure is not infrequent outside the B. abortus and B. melitensis clusters and that it represents a new and extended Brucella serovar.…”

Section: Resultssupporting

confidence: 73%

The Epitopic and Structural Characterization of Brucella suis Biovar 2 O-Polysaccharide Demonstrates the Existence of a New M-Negative C-Negative Smooth Brucella Serovar

et al. 2013

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The brucellae are Gram-negative bacteria that cause an important zoonosis. Studies with the main Brucella species have shown that the O-antigens of the Brucella smooth lipopolysaccharide are α-(1→2) and α-(1→3)-linked N-formyl-perosamine polysaccharides that carry M, A and C (A = M, A>M and AA) and M specificities. However, the biovar 2 O-antigen bound monoclonal antibodies to the Brucella A epitope, and to the C/Y epitope shared by brucellae and Yersinia enterocolitica O:9, a bacterium that carries an N-formyl-perosamine O-antigen in exclusively α-(1→2)-linkages. By 13C NMR spectroscopy, B. suis biovar 1 but not B. suis biovar 2 or Y. enterocolitica O:9 polysaccharide showed the signal characteristic of α-(1→3)-linked N-formyl-perosamine, indicating that biovar 2 may altogether lack this linkage. Taken together, the NMR spectroscopy and monoclonal antibody analyses strongly suggest a role for α-(1→3)-linked N-formyl-perosamine in the C (A = M) and C (M>A) epitopes. Moreover, they indicate that B. suis biovar 2 O-antigen lacks some lipopolysaccharide epitopes previously thought to be present in all smooth brucellae, thus representing a new brucella serovar that is M-negative, C-negative. Serologically and structurally this new serovar is more similar to Y. enterocolitica O:9 than to other brucellae.

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Section: Resultssupporting

confidence: 73%

The Epitopic and Structural Characterization of Brucella suis Biovar 2 O-Polysaccharide Demonstrates the Existence of a New M-Negative C-Negative Smooth Brucella Serovar

et al. 2013

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“…This is likely related to the composition of LPS in the classical species that differs from the conventional LPS structure found in other gram(-) bacterial pathogens (Cardoso et al, 2006). In this regard, it has been shown that the core-lipid A moiety of LPS of B. microti is different from classical Brucella spp., although its ability to activate TLR4 has not been tested yet (Zygmunt et al, 2012). Further supporting this hypothesis, it is well known that TLR2 and TLR4 are crucial in host defense against several bacterial pathogens that, like B. microti , cause sepsis like Staphylococcus aureus, Streptococcus pneumoniae (Takeuchi et al, 2000; Dessing et al, 2008), Klebsiella pneumoniae (Schurr et al, 2005), Haemophillus influenza (Wang et al, 2002) and Acinetobacter baumanii (Knapp et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Toll-Like Receptors 2 and 4 Cooperate in the Control of the Emerging Pathogen Brucella microti

Arias

Santiago

Costas-Ramon

et al. 2017

Front. Cell. Infect. Microbiol.

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Toll-like receptors (TLRs) recognize pathogen-derived molecules and play a critical role during the host innate and adaptive immune response. Brucella spp. are intracellular gram-negative bacteria including several virulent species, which cause a chronic zoonotic infection in a wide range of mammalian hosts known as brucellosis. A new Brucella species, Brucella microti, was recently isolated from wild rodents and found to be highly pathogenic in mice. Using this species-specific model, it was previously found that CD8+ T cells are required to control this infection. In order to find out the role of TLR-mediated responses in the control of this pathogen, the course of infection of B. microti was analyzed over 3 weeks in wild-type (WT) and TLR knock out (KO) mice including TLR2−/−, TLR4−/−, TLR9−/−, TLR2×4−/− and TLR2×4×9−/−. WT and single TLR2, TLR4 and TLR9 KO mice similarly control infection in liver and spleen. In contrast, bacterial clearance was delayed in TLR2×4−/− and TLR2×4×9−/− mice at 7 and 14 days post-infection. This defect correlated with impaired maturation and pro-inflammatory cytokine production in B. microti-infected dendritic cells from TLR2×4−/− and TLR2×4×9−/− mice. Finally, it was found that Tc cells from TLR2×4−/− and TLR2×4×9−/− mice showed reduced ability to inhibit growth of B. microti in macrophages, suggesting the involvement of TLR2 and 4 in the generation of specific Tc cells. Our findings indicate that TLR2 and TLR4 are required to control B. microti infection in mice and that this effect could be related to its participation in the maturation of dendritic cells and the generation of specific CD8+ Tc cells.

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“…Perhaps the same occurred for the B. suis 145 extracellular fraction in that some of its LPS resisted acid-heat hydrolysis, protecting a PS antigen that provided additional vaccine efficacy. Such an antigen could be a different A or M antigen similar to different A antigens observed for B. abortus and Yersinia enterocolitica O:9 (25), an additional "soluble supernatant substance" or "S antigen" proposed by researchers in the 1930s (26), or more recently the reported novel PS antigens of B. suis (27,28). These possibilities could also explain how CE showed that anti-A, anti-M, and anti-A/M/C monoclonal antibodies bound to cell-associated PS fractions B2 and B3 but not the extracellular fraction B1 and how the subunit vaccine fractionated by pH had the two most effective fractions at the lowest and highest pI.…”

Section: Discussionmentioning

confidence: 96%

Thermostable Cross-Protective Subunit Vaccine against Brucella Species

Cherwonogrodzky

Barabé

Grigat

et al. 2014

Clin Vaccine Immunol

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A subunit vaccine candidate was produced from Brucella suis 145 (biovar 4; expressing both the A antigen of Brucella abortus and the M antigen of Brucella melitensis). The preparation consisted mostly of polysaccharide (PS; >90% [wt/wt]; both cell-associated PS and exo-PS were combined) and a small amount of protein (1 to 3%) with no apparent nucleic acids. Vaccinated mice were protected (these had a statistically significant reduction in bacterial colonization compared to that of unvaccinated controls) when challenged with representative strains of three Brucella species most pathogenic for humans, i.e., B. abortus, B. melitensis, and B. suis. As little as 1 ng of the vaccine, without added adjuvant, protected mice against B. suis 145 infection (5 ؋ 10 5 CFU), and a single injection of 1 g of this subunit vaccine protected mice from B. suis 145 challenge for at least 14 months. A single immunization induced a serum IgG response to Brucella antigens that remained elevated for up to 9 weeks. The use of heat (i.e., boiling-water bath, autoclaving) in the vaccine preparation showed that it was thermostable. This method also ensured safety and security. The vaccine produced was immunogenic and highly protective against multiple strains of Brucella and represents a promising candidate for further evaluation.

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Lipopolysaccharide Heterogeneity in the Atypical Group of Novel Emerging Brucella Species

Abstract: ABSTRACTRecently, novelBrucellastrains with phenotypic characteristics that were atypical for strains belonging to the genusBrucellahave been reported. Phenotypically many of these strains were initially misidentified asOchrobactrumspp. Two novel species have been describ… Show more

Cited by 34 publications

References 36 publications

The Epitopic and Structural Characterization of Brucella suis Biovar 2 O-Polysaccharide Demonstrates the Existence of a New M-Negative C-Negative Smooth Brucella Serovar

The Epitopic and Structural Characterization of Brucella suis Biovar 2 O-Polysaccharide Demonstrates the Existence of a New M-Negative C-Negative Smooth Brucella Serovar

Toll-Like Receptors 2 and 4 Cooperate in the Control of the Emerging Pathogen Brucella microti

Thermostable Cross-Protective Subunit Vaccine against Brucella Species

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