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

Lauren W Stranahan,Angela M Arenas-Gamboa

doi:10.3389/fmicb.2021.713157

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.

Highlights

Despite knowledge of its existence for over a century, brucellosis remains one of the most commonly reported zoonotic diseases worldwide (Pappas et al, 2006)
Work with B. canis has highlighted that the choice of adjuvant can significantly impact the efficacy of a subunit vaccine (Clausse et al, 2014) and studies involving both natural rough strains have demonstrated improved protection of certain live attenuated vaccine (LAV) when given in an encapsulated form, as has been shown for smooth Brucella spp
Lacking in O-PS, B. canis and B. ovis are virulent pathogens in their natural hosts that are able to recapitulate many of the properties and cellular interactions observed by their more famous smooth cousins

Summary

Introduction

Despite knowledge of its existence for over a century, brucellosis remains one of the most commonly reported zoonotic diseases worldwide (Pappas et al, 2006). The T4SS appears to be just as important for allowing intracellular replication in the natural roughs as in the smooths as mutants in virB genes or vjbR of B. ovis and B. canis exhibit significant attenuation and inability to replicate within ovine macrophages and mice or HeLa cells, murine RAW 264.7 macrophages, and canine DH82 dendritic cells, respectively (Sá et al, 2012; Chacón-Díaz et al, 2015; Macedo et al, 2015; Stranahan et al, 2020).

Results

Conclusion