When the Going Gets Rough: The Significance of Brucella Lipopolysaccharide Phenotype in Host–Pathogen Interactions

Abstract

Brucella is a facultatively intracellular bacterial pathogen and the cause of worldwide zoonotic infections, infamous for its ability to evade the immune system and persist chronically within host cells. Despite the frequent association with attenuation in other Gram-negative bacteria, a rough lipopolysaccharide phenotype is retained by Brucella canis and Brucella ovis, which remain fully virulent in their natural canine and ovine hosts, respectively. While these natural rough strains lack the O-polysaccharide they, like their smooth counterparts, are able to evade and manipulate the host immune system by exhibiting low endotoxic activity, resisting destruction by complement and antimicrobial peptides, entering and trafficking within host cells along a similar pathway, and interfering with MHC-II antigen presentation. B. canis and B. ovis appear to have compensated for their roughness by alterations to their outer membrane, especially in regards to outer membrane proteins. B. canis, in particular, also shows evidence of being less proinflammatory in vivo, suggesting that the rough phenotype may be associated with an enhanced level of stealth that could allow these pathogens to persist for longer periods of time undetected. Nevertheless, much additional work is required to understand the correlates of immune protection against the natural rough Brucella spp., a critical step toward development of much-needed vaccines. This review will highlight the significance of rough lipopolysaccharide in the context of both natural disease and host–pathogen interactions with an emphasis on natural rough Brucella spp. and the implications for vaccine development.

The Transcriptional Regulator MucR, but Not Its Controlled Acid-Activated Chaperone HdeA, Is Essential for Virulence and Modulates Surface Architecture and Properties in Brucella ovis PA

“…Ovine brucellosis is mainly caused by Brucella melitensis and Brucella ovis , species that share high levels of homology at the DNA level ( 3 ) but exhibit relevant differences regarding pathogenicity. Thus, B. melitensis induces abortion in the natural host, is the most relevant zoonotic Brucella species ( 4 ), and is defined as smooth because it bears O-polysaccharide chains in the lipopolysaccharide (LPS), which are required for full virulence ( 5 , 6 ). On the contrary, B. ovis is rough (lacks O-chains in the LPS), has never been reported as a human pathogen, and rarely induces abortion in sheep.…”

“…The surface of bacterial pathogens is a key structure connecting the cell with the surrounding environment, including host cells and defense mechanisms. The LPS O-chains are essential for virulence in smooth brucellae ( 5 , 6 ), and it is known that they mask other surface components ( 5 , 17 ). Considering the rough nature of B. ovis , molecules exposed on the bacterial surface and/or regulatory mechanisms affecting its structure could be relevant actors in host–pathogen interactions, targets for the development of attenuated vaccines and related to the differences in pathogenicity and host preference that exist in the genus Brucella .…”

“…Considering the rough nature of B. ovis , molecules exposed on the bacterial surface and/or regulatory mechanisms affecting its structure could be relevant actors in host–pathogen interactions, targets for the development of attenuated vaccines and related to the differences in pathogenicity and host preference that exist in the genus Brucella . In fact, in addition to the presence or absence of O-chains in the LPS, the Brucella species differ in outer membrane (OM) composition ( 5 , 6 , 18 ) and OM-related properties ( 5 , 6 , 19 ).…”

Complete Lipopolysaccharide of Piscirickettsia salmonis Is Required for Full Virulence in the Intraperitoneally Challenged Atlantic Salmon, Salmo salar, Model

“…So as to explain the reduced susceptibility to polymyxin B manifested by P. salmonis, we may refer to findings obtained in naturally virulent, rough species of the Brucella genus. These pathogens have a truncated O-chain LPS and are not only resistant to the action of complement, but also to that of positively charged antimicrobial peptides, including polymyxin B (Stranahan and Arenas-Gamboa, 2021). Taking into account these precedents, our results obtained in serum survival and polymyxin B MIC tests may be related to P. salmonis having evolved carrying an LPS with an atypical short O-antigen, suggesting that the LOS structure conferred an evolutionary advantage to this pathogen.…”

Genomic Characterization of Aureimonas altamirensis C2P003—A Specific Member of the Microbiome of Fraxinus excelsior Trees Tolerant to Ash Dieback

“…The genes for T4SS transfer proteins could also be detected in the genomes of the Aureimonas strains C2P003, DSM 21988 and ON-56566 (Tables 2 and S1). Further virulence factors of Brucella, in particular genes involved in the biosynthesis of the lipopolysaccharide O-side chain (e.g., wboA, wboB, wbkA, wbkE, gmd) [45], could not be identified in the genome of any Aureimonas strains. The phenotypic tests with strain C2P003 did not indicate a pathogenic potential.…”