Pathogenesis and Immunobiology of Brucellosis

Abstract

This review of Brucellaehost interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat brucellosis. Brucella spp., as animal pathogens, cause human brucellosis, a zoonosis that results in worldwide economic losses, human morbidity, and poverty. Although Brucella spp. infect humans as an incidental host, 500,000 new human infections occur annually, and no patient-friendly treatments or approved human vaccines are reported. Brucellae display strong tissue tropism for lymphoreticular and reproductive systems with an intracellular lifestyle that limits exposure to innate and adaptive immune responses, sequesters the organism from the effects of antibiotics, and drives clinical disease manifestations and pathology. Stealthy brucellae exploit strategies to establish infection, including i) evasion of intracellular destruction by restricting fusion of type IV secretion systemdependent Brucella-containing vacuoles with lysosomal compartments, ii) inhibition of apoptosis of infected mononuclear cells, and iii) prevention of dendritic cell maturation, antigen presentation, and activation of naive T cells, pathogenesis lessons that may be informative for other intracellular pathogens. Data sets of next-generation sequences of Brucella and host time-series global expression fused with proteomics and metabolomics data from in vitro and in vivo experiments now inform interactive cellular pathways and gene regulatory networks enabling full-scale systems biology analysis. The newly identified effector proteins of Brucella may represent targets for improved, safer brucellosis vaccines and therapeutics. It is noteworthy that long ago in his publication Epidemics, Hippocrates described brucellosis-type syndromes in humans living in the Mediterranean littoral. Many centuries later, British physician, David Bruce, and Greek physician, Themistokles Zammit, in 1886 would discover the causative agent, Micrococcus melitensis, of brucellosis and would identify milk products of goats as the source of infection for military troops on the island of Malta. Even after more than a century of extensive research, Brucella spp. are still serious animal pathogens that cause brucellosis, a zoonosis that results in substantial economic losses, human morbidity, and perpetuates poverty worldwide.1 These Gram-negative bacteria infect a diverse array of land and aquatic mammals,

The Role of Apoptosis and Autophagy in Bovine Abortions Associated with Brucella Spp

“…The appearance of autophagic Brucella-containing vacuoles over time involves the acquisition of several autophagy proteins, such as Unc-51-like kinase 1 and Beclin 1. ATG5 and LC3B have been reported in autophagicBrucella-containing vacuoles [38,39]. In the present study, immune positivity for LC3B was directly correlated to the distribution and intensity of the antigen in all the examined organs.…”

A Simple and Safe Protocol for Preparing Brucella Samples for Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry Analysis

“…rucellosis is a zoonosis caused by bacteria of the genus Brucella, which are transmitted to humans through direct contact, ingestion of contaminated animal products, or aerosolization (1,2). Brucellosis is endemic in several regions of the world, with more than 500,000 new cases each year (2)(3)(4)(5).…”

Genomic analysis of the original Elberg Brucella melitensis Rev.1 vaccine strain reveals insights into virulence attenuation

“…Facultative intracellular Brucella are known to be capable of employing various strategies to survive the bactericidal environment within phagocytes and, thereby, to avoid the immune system of the host [32]. During this process, molecular chaperones, peroxiredoxins, and siderophores were shown to play an important role in Brucella survival [33–35].…”

“…To survive extreme environmental changes and respond well to various stress conditions within their hosts, Brucella require a suitable regulation system [32]. Our SNP analysis revealed missense mutations in the ORF BMEI0685 (c.896C> G and c.884C> T), which encodes an AraC-like transcriptional regulator, and in the ORF BMEI1816 (c.443G> C), encoding the sensor histidine kinase RegB two-component system.…”