Lipopolysaccharide as a target for brucellosis vaccine design

Conde-Álvarez, Raquel; Arce‐Gorvel, Vilma; Gil-Ramírez, Yolanda; Iriarte, Maite; Grilló, María Jesús; Gorvel, Jean‐Pierre; Moriyón, Ignacio

doi:10.1016/j.micpath.2012.11.011

Cited by 31 publications

(28 citation statements)

References 27 publications

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“…Other matches showed less than 35% homology, the threshold below which protein sequence alignment becomes meaningless [8,23]. Of these three ORFs, B. abortus BAB1_1522 encodes WadC and B. abortus BAB1_0639 encodes WadA, the only two core glycosyltransferases described previously [7,9,24]. Their identification supported the appropriateness of the screening method and, accordingly, the remaining ORF (BAB1_0351) was a strong candidate for an additional core glycosyltransferase.…”

Section: Identification Of Wadb a Glycosyltransferase Gene Involved mentioning

confidence: 60%

“…We have proposed before that disruption of the structure of the Brucella LPS core can be exploited to develop vaccines that would elicit the early innate immunity recognition that leads to Th1 protective responses [24]. Although vaccine S19 has been successfully used in developed countries for the control and eradication of cattle brucellosis, the protection achieved is not optimal [30] and success using this vaccine requires a very proficient veterinary infrastructure.…”

Section: Discussionmentioning

confidence: 99%

“…Although vaccine S19 has been successfully used in developed countries for the control and eradication of cattle brucellosis, the protection achieved is not optimal [30] and success using this vaccine requires a very proficient veterinary infrastructure. Previous experiments in the mouse model suggest that the B. abortus wadC core mutations could be either introduced in S19 to reduce its residual virulence but bolstering its immunogenic properties or in a wild-type background, in combination with other appropriate mutations, to develop improved vaccines [24]. In this context, the identification of wadB adds another target for the development of new generation anti-Brucella vaccines less pathogenic and more immunogenic than currently available vaccines A study of the vaccine properties of wadB and wadC mutants in various Brucella backgrounds is in progress.…”

Section: Discussionmentioning

confidence: 99%

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The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus

Gil-Ramírez

Conde-Álvarez

Palacios-Chaves

et al. 2014

Microbial Pathogenesis

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Brucellosis is a worldwide extended zoonosis caused by Brucella spp. These gram-negative bacteria are not readily detected by innate immunity, a virulence-related property largely linked to their surface lipopolysaccharide (LPS). The role of the LPS lipid A and O-polysaccharide in virulence is well known. Moreover, mutation of the glycosyltransferase gene wadC of B. abortus, although not affecting O-polysaccharide assembly onto the lipid-A core section causes a core oligosaccharide defect that increases recognition by innate immunity. Here, we report on a second gene (wadB) encoding a LPS core glycosyltransferase not involved in the assembly of the O-polysaccharide-linked core section. As compared to wild-type B. abortus, a wadB mutant was sensitive to bactericidal peptides and non-immune serum, and was attenuated in mice and dendritic cells. These observations show that as WadC, WadB is also involved in the assembly of a branch of Brucella LPS core and support the concept that this LPS section is a virulence-related structure.4

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Section: Identification Of Wadb a Glycosyltransferase Gene Involved mentioning

confidence: 60%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus

Gil-Ramírez

Conde-Álvarez

Palacios-Chaves

et al. 2014

Microbial Pathogenesis

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“…In addition, the core oligosaccharide section has been shown recently to hamper recognition by innate immunity systems, including complement, bactericidal peptides and the TLR4-MD2 complex [5]. It has been postulated that the Brucella S-LPS core carries a lateral branch that hinders access of innate immunity effector proteins and receptors to the inner sections of the core and lipid A [5][6][7], and the existence of a branched structure has been confirmed by structural analysis (Figure 1) [8]. These findings have opened the way for an analysis of the role of the LPS of R Brucella species in virulence.…”

Section: Introductionmentioning

confidence: 99%

“…These findings have opened the way for an analysis of the role of the LPS of R Brucella species in virulence. Moreover, as delayed recognition by innate immunity plays a major role in Brucella virulence, core mutants represent candidates for the development of vaccines triggering an early and thus protective immunoresponse [6].…”

Section: Introductionmentioning

confidence: 99%

Mutants in the lipopolysaccharide of

Soler-Lloréns

Gil-Ramírez

Zabalza-Baranguá

et al. 2014

Vet Res

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Brucella spp. are Gram-negative bacteria that behave as facultative intracellular parasites of a variety of mammals. This genus includes smooth (S) and rough (R) species that carry S and R lipopolysaccharides (LPS), respectively. S-LPS is a virulence factor, and mutants affected in the S-LPS O-polysaccharide (R mutants), core oligosaccharide or both show attenuation. However, B. ovis is naturally R and is virulent in sheep. We studied the role of B. ovis LPS in virulence by mutating the orthologues of wadA, wadB and wadC, three genes known to encode LPS core glycosyltransferases in S brucellae. When mapped with antibodies to outer membrane proteins (Omps) and R-LPS, wadB and wadC mutants displayed defects in LPS structure and outer membrane topology but inactivation of wadA had little or no effect. Consistent with these observations, the wadB and wadC but not the wadA mutants were attenuated in mice. When tested as vaccines, the wadB and wadC mutants protected mice against B. ovis challenge. The results demonstrate that the LPS core is a structure essential for survival in vivo not only of S brucellae but also of a naturally R Brucella pathogenic species, and they confirm our previous hypothesis that the Brucella LPS core is a target for vaccine development. Since vaccine B. melitensis Rev 1 is S and thus interferes in serological testing for S brucellae, wadB mutant represents a candidate vaccine to be evaluated against B. ovis infection of sheep suitable for areas free of B. melitensis.

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New Features in the Lipid A Structure of Brucella suis and Brucella abortus Lipopolysaccharide

Casabuono

Czibener

Giudice

et al. 2017

J. Am. Soc. Mass Spectrom.

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Brucellaceae are Gram-negative bacteria that cause brucellosis, one of the most distributed worldwide zoonosis, transmitted to humans by contact with either infected animals or their products. The lipopolysaccharide exposed on the cell surface has been intensively studied and is considered a major virulence factor of Brucella. In the last years, structural studies allowed the determination of new structures in the core oligosaccharide and the O-antigen of this lipopolysaccharide. In this work, we have reinvestigated the lipid A structure isolated from B. suis and B. abortus lipopolysaccharides. A detailed study by MALDI-TOF mass spectrometry in the positive and negative ion modes of the lipid A moieties purified from both species was performed. Interestingly, a new feature was detected: the presence of a pyrophosphorylethanolamine residue substituting the backbone. LID-MS/MS analysis of some of the detected ions allowed assurance that the Lipid A structure composed by the diGlcN3N disaccharide, mainly hexa-acylated and penta-acylated, bearing one phosphate and one pyrophosphorylethanolamine residue. Graphical abstract ᅟ.

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Lipopolysaccharide as a target for brucellosis vaccine design

Cited by 31 publications

References 27 publications

The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus

The identification of wadB, a new glycosyltransferase gene, confirms the branched structure and the role in virulence of the lipopolysaccharide core of Brucella abortus

Mutants in the lipopolysaccharide of

New Features in the Lipid A Structure of Brucella suis and Brucella abortus Lipopolysaccharide

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