Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

Abstract

Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

Pathogenesis and Immunobiology of Brucellosis

“…6,8,13,16,18,32,53e60 This broad spectrum of data sets was analyzed to identify candidate genes and biomarkers of Brucella and hosts, 61 to analyze 62 and predict Brucella antigenic proteins, to identify subunit vaccines, 63 to understand gene regulatory networks, 54 and to characterize the stringent Brucella stress response 64 and modulation of host responses. 53 Time-series studies of in vitro or in vivo experimental infection data were performed with a systems-based perspective of complex biological organizations to categorize the interactions of individual proteins within Brucellaehost proteine protein networks. Time-series studies of in vivo system have…”

RNA-seq reveals the critical role of CspA in regulating Brucella melitensis metabolism and virulence

“…The ability of brucellae to survive within macrophages is essential for their virulence (Celli and Gorvel, 2004). In the past few years, hundreds of virulence-related genes have been identified by transposon mutagenesis (Wu et al, 2006), in vivo-induced antigen technology (Lowry et al, 2011), DNA microarray hybridization (Tian et al, 2013), and bioinformatics (He, 2012), which include lipopolysaccharide (Seleem et al, 2008), the type IV secretion system T4SS (Seleem et al, 2008;Martirosyan et al, 2011), the quorum-sensing-related transcriptional regulator VjbR , the BvrR/BvrS two-component regulatory system (Sola-Landa et al, 1998;Martinez-Nunez et al, 2010), and the periplasmic cyclic -1,2 glucans (Briones et al, 2001), among others. Interestingly, most of these genes are not direct virulence factors, but are transcription regulators, such as VjbR which can control the expression of virulence factors to affect Brucella virulence .…”

Current Methods of Human and Animal Brucellosis Diagnostics

“…It seems like that there is no single universal immunodominant protein, but up-to-date proteomic methods allow analysis of the whole Brucella proteome in order to identify a series of such proteins. The methods of system biology can not only be successfully used in the diagnosis of brucellosis, but they can expand the understanding of fundamental biological processes in the Brucella infected organism, including those leading to the great variety in the immune response [61].…”