Abstract
Many virulence genes have been detected in attenuated mutants of Brucella melitensis 16 M; nevertheless, a complete report of these genes, including the main Cluster of Orthologous Groups (COG) represented as well as the taxonomical distribution among all complete bacterial and archaeal genomes, has not been analyzed. In this work a total of 160 virulence genes that have been reported in attenuated mutants in B. melitensis were included and analyzed. Additionally, we obtained 250 B. melitensis randomly selected genes as a reference group for the taxonomical comparisons. The COGs and the taxonomical distribution profile for 789 nonredundant bacterial and archaeal genomes were obtained and compared with the whole-genome COG distribution and with the 250 randomly selected genes, respectively. The main COGs associated with virulence genes corresponded to the following: intracellular trafficking, secretion and vesicular transport (U); cell motility (N); nucleotide transport and metabolism (F); transcription (K); and cell wall/membrane/envelope biogenesis (M). In addition, we found that virulence genes presented a higher proportion of orthologs in the Euryarchaeota and Proteobacteria phyla, with a significant decrease in Chlamydiae, Bacteroidetes, Tenericutes, Firmicutes and Thermotogae. In conclusion, we found that genes related to specific functions are more relevant to B. melitensis virulence, with the COG U the most significant. Additionally, the taxonomical distribution of virulence genes highlights the importance of these genes in the related Proteobacteria, being less relevant in distant groups of organisms with the exception of Euryarchaeota.
Highlights
Bacteria of the genus Brucella are the etiological agents of brucellosis, the most widely spread zoonotic disease worldwide
In the comparison of virulence genes with the wholegenome Cluster of Orthologous Groups (COG) distribution, we found a significant overrepresentation of the COGs for intracellular trafficking, secretion and vesicular transport (U) (7.81% vs 1.5%), nucleotide transport and metabolism (F) (6.56% vs 2.2%), cell motility (N) (4.69% vs 0.92%), transcription (K) (10.44% vs 5.62%) and cell wall/ membrane/envelope biogenesis (M) (10.62% vs 5.0%) and an underrepresentation of genes not categorized in a COG (NC) (Table 2)
The difference was more significant for COGs U, N and F, which are composed mainly of genes grouped in the virB operon, flagellar genes and genes for enzymes related to nucleotide synthesis, respectively; COG M includes predominantly genes for enzymes related to lipopolysaccharide production, while COG K was mainly represented by RNA polymerase sigma factors and transcription factors of the families MerR, LysR, LuxR, AsnC and GntR (Table 1)
Summary
Bacteria of the genus Brucella are the etiological agents of brucellosis, the most widely spread zoonotic disease worldwide. B. melitensis is a Gram-negative facultative intracellular pathogen that belongs to the alpha-2 proteobacteria group This bacterium has the ability to infect phagocytic macrophages and nonphagocytic cells (epithelial cells, fibroblasts and osteoblasts), and its virulence relies on the ability to replicate inside these cells [5,6]. Brucella lacks known bacterial pathogenic factors that can directly harm eukaryotic cells, such as cytolisins, exotoxins, exoproteases and exoenzymes, nor does it express pathogenic determinants, like fimbriae, capsules, antigenic variation and plasmids [5,6]. All these data suggest that the bacterium produces direct tissue damage, probably by the activation of host immune responses [5]. An integrative analysis of these genes in B. melitensis has not been addressed; the main goal of this work is to achieve a comprehensive comparison of virulencerelated genes identified in B. melitensis 16 M under different approaches, to gain insights into their main functions and their taxonomical distribution across bacterial and archaeal genomes
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