Mutants in the Lipopolysaccharide of Brucella Ovis Are Attenuated and Protect Against B. Ovis Infection in Mice

Overview

Journal Vet Res

Publisher Biomed Central

Specialty Veterinary Medicine

Date 2014 Jul 18

PMID 25029920

Citations 23

Authors

Pedro Soler-Llorens

Yolanda Gil-Ramirez

Ana Zabalza-Barangua

Maite Iriarte

Raquel Conde-Alvarez

Amaia Zuniga-Ripa

Beatriz San Roman

Michel S Zygmunt

Nieves Vizcaino

Axel Cloeckaert

Maria-Jesus Grillo

Ignacio Moriyon

Ignacio Lopez-Goni

Affiliations

Soon will be listed here.

Abstract

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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