Abstract
Brucellosis is one of the most common zoonotic epidemics with a serious threat to public health and livestock development in many countries across the world. Vaccination is a key control strategy toward preventing brucellosis in high-prevalence regions. Recently, a rough-type Brucella melitensis mutant strain (RM57) induced from a B. melitensis strain M1981 showed protective effects in guinea pigs indicating that it is a good vaccine candidate. In this study, stress response assays were performed to reveal the mechanisms underlying virulence attenuation of RM57. In addition, a genome-wide transcriptome profile of RM57 was analyzed relative to the parent strain M1981 in order to reveal genetic factors controlling the phenotypes. Our results indicated a similar sensitivity to various stress conditions in RM57 owing to a lack of significant differences from its parent strain. Transcriptome analysis showed that a total of 1,205 genes were differentially expressed between RM57 and M1981 with gene ontology terms revealing that these genes are involved in energy production and conversion, translation, ribosomal structure, and biogenesis. Pathway enrichment analysis revealed that genes involved in oxidative phosphorylation, ribosome, nitrogen metabolism, tyrosine metabolism, and two-component system were significantly affected. As a result of these differences at the molecular level, the function of type IV secretion system in RM57 was found to be affected leading to reduced virulence of the RM57 mutant strain in both macrophage and mice infection models.
Highlights
Brucellosis, an infectious disease caused by Brucella spp. and spreads through unpasteurized dairy products, remains one of the most serious bacterial zoonosis across the world
Various studies have demonstrated that live Brucella vaccines such as S19, RB51, S2, and Rev.1 are able to effectively offer immune protection against brucellosis and these are widely used around the world [4]
As RM57 was attenuated in mice and guinea pig infection models and showed promise as an ideal vaccine candidate, we aimed to unravel the mechanism of virulence attenuation of the RM57 strain through phenotypic characterization and transcriptome analysis
Summary
Brucellosis, an infectious disease caused by Brucella spp. and spreads through unpasteurized dairy products, remains one of the most serious bacterial zoonosis across the world. In animals, this pathogen mainly causes abortion in females and male infertility various other clinical symptoms including fever, night sweats, anorexia, polyarthritis, meningitis, and pneumonia have been reported in humans. Vaccination has been successful as a control strategy for preventing exposure to brucellosis in regions where the disease is prevalent [3]. Negative implications of these vaccines including diagnostic interference, residual virulence in the host, and pathogenic effects to human health cast doubts to this control strategy [3, 5,6,7]
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