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Frontiers in Cellular and Infection... 2012Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species,... (Review)
Review
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.
Topics: Animals; Antigens, Bacterial; Brucella; Brucella Vaccine; Computational Biology; Genomics; Humans; Proteomics; Systems Biology; Transcriptome; Virulence Factors
PubMed: 22919594
DOI: 10.3389/fcimb.2012.00002 -
Emerging Infectious Diseases 1997Brucellosis remains a major zoonosis worldwide. Although many countries have eradicated Brucella abortus from cattle, in some areas Brucella melitensis has emerged as a... (Review)
Review
Brucellosis remains a major zoonosis worldwide. Although many countries have eradicated Brucella abortus from cattle, in some areas Brucella melitensis has emerged as a cause of infection in this species as well as in sheep and goats. Despite vaccination campaigns with the Rev 1 strain, B. melitensis remains the principal cause of human brucellosis. Brucella suis is also emerging as an agent of infection in cattle, thus extending its opportunities to infect humans. The recent isolation of distinctive strains of Brucella from marine mammals has extended its ecologic range. Molecular genetic studies have demonstrated phylogenetic affiliation to Agrobacterium, Phyllobacterium, Ochrobactrum, and Rhizobium. Polymerase chain reaction and gene probe development may provide more effective typing methods. Pathogenicity is related to production of lipopolysaccharides containing a poly N-formyl perosamine O chain, CuZn superoxide dismutase, erythrlose phosphate dehydrogenase, stress-induced proteins related to intracellular survival, and adenine and guanine monophosphate inhibitors of phagocyte functions. Protective immunity is conferred by antibody to lipopolysaccharide and T-cell-mediated macrophage activation triggered by protein antigens. Diagnosis still centers on isolation of the organism and serologic test results, especially enzyme immunoassay, which is replacing other methods. Polymerase chain reaction is also under evaluation. Therapy is based on tetracyclines with or without rifampicin, aminoglycosides, or quinolones. No satisfactory vaccines against human brucellosis are available, although attenuated purE mutants appear promising.
Topics: Animals; Antigens, Bacterial; Brucella; Brucellosis; Cattle; Humans
PubMed: 9204307
DOI: 10.3201/eid0302.970219 -
International Journal of Molecular... Jun 2023, the causative agent of brucellosis, poses a significant public health and animal husbandry threat. However, the role of the alanine racemase () gene, which encodes...
, the causative agent of brucellosis, poses a significant public health and animal husbandry threat. However, the role of the alanine racemase () gene, which encodes alanine racemase in , remains unclear. Here, we analyzed an deletion mutant and a complemented strain of S2. The knockout strain displayed an unaltered, smooth phenotype in acriflavine agglutination tests but lacked the core polysaccharide portion of lipopolysaccharide (LPS). Genes involved in the LPS synthesis were significantly upregulated in the deletion mutant. The deletion strain exhibited reduced intracellular viability in the macrophages, increased macrophage-mediated killing, and upregulation of the apoptosis markers. Bcl2, an anti-apoptotic protein, was downregulated, while the pro-apoptotic proteins, Bax, Caspase-9, and Caspase-3, were upregulated in the macrophages infected with the deletion strain. The infected macrophages showed increased mitochondrial membrane permeability, Cytochrome C release, and reactive oxygen species, activating the mitochondrial apoptosis pathway. These findings revealed that alanine racemase was dispensable in S2 but influenced the strain's rough features and triggered the mitochondrial apoptosis pathway during macrophage invasion. The deletion of the gene reduced the intracellular survival and virulence. This study enhances our understanding of the molecular mechanism underlying 's survival and virulence and, specifically, how gene affects host immune evasion by regulating bacterial LPS biosynthesis.
Topics: Animals; Brucella suis; Lipopolysaccharides; Virulence; Alanine Racemase; Brucellosis
PubMed: 37445922
DOI: 10.3390/ijms241310744 -
Pathogens (Basel, Switzerland) Nov 2020A central aspect of pathogenicity is its ability to invade, survive, and replicate in diverse phagocytic and non-phagocytic cell types, leading to chronic infections... (Review)
Review
A central aspect of pathogenicity is its ability to invade, survive, and replicate in diverse phagocytic and non-phagocytic cell types, leading to chronic infections and chronic inflammatory phenomena. Adhesion to the target cell is a critical first step in the invasion process. Several adhesins have been shown to mediate adhesion to cells, extracellular matrix components (ECM), or both. These include the sialic acid-binding proteins SP29 and SP41 (binding to erythrocytes and epithelial cells, respectively), the BigA and BigB proteins that contain an Ig-like domain (binding to cell adhesion molecules in epithelial cells), the monomeric autotransporters BmaA, BmaB, and BmaC (binding to ECM components, epithelial cells, osteoblasts, synoviocytes, and trophoblasts), the trimeric autotransporters BtaE and BtaF (binding to ECM components and epithelial cells) and Bp26 (binding to ECM components). An in vivo role has also been shown for the trimeric autotransporters, as deletion mutants display decreased colonization after oral and/or respiratory infection in mice, and it has also been suggested for BigA and BigB. Several adhesins have shown unipolar localization, suggesting that would express an adhesive pole. Adhesin-based vaccines may be useful to prevent brucellosis, as intranasal immunization in mice with BtaF conferred high levels of protection against oral challenge with .
PubMed: 33198223
DOI: 10.3390/pathogens9110942 -
Frontiers in Microbiology 2018Bacteria of the genus infect a range of vertebrates causing a worldwide extended zoonosis. The best-characterized brucellae infect domestic livestock, behaving as...
The Fast-Growing Biovar 5 Depends on Phosphoenolpyruvate Carboxykinase and Pyruvate Phosphate Dikinase but Not on Fbp and GlpX Fructose-1,6-Bisphosphatases or Isocitrate Lyase for Full Virulence in Laboratory Models.
Bacteria of the genus infect a range of vertebrates causing a worldwide extended zoonosis. The best-characterized brucellae infect domestic livestock, behaving as stealthy facultative intracellular parasites. This stealthiness depends on envelope molecules with reduced pathogen-associated molecular patterns, as revealed by the low lethality and ability to persist in mice of these bacteria. Infected cells are often engorged with brucellae without signs of distress, suggesting that stealthiness could also reflect an adaptation of the parasite metabolism to use local nutrients without harming the cell. To investigate this, we compared key metabolic abilities of 2308 Wisconsin (2308W), a cattle biovar 1 virulent strain, and 513, the reference strain of the ancestral biovar 5 found in wild rodents. 513 used a larger number of C substrates and showed faster growth rates , two features similar to those of , a species phylogenomically close to biovar 5 that infects voles. However, whereas shows enhanced lethality and reduced persistence in mice, 513 was similar to 2308W in this regard. Mutant analyses showed that 513 and 2308W were similar in that both depend on phosphoenolpyruvate synthesis for virulence but not on the classical gluconeogenic fructose-1,6-bisphosphatases Fbp-GlpX or on isocitrate lyase (AceA). However, 513 used pyruvate phosphate dikinase (PpdK) and phosphoenolpyruvate carboxykinase (PckA) for phosphoenolpyruvate synthesis while 2308W used only PpdK. Moreover, whereas PpdK dysfunction causes attenuation of 2308W in mice, in , 513 attenuation occurred only in the double PckA-PpdK mutant. Also contrary to what occurs in 2308, a 513 malic enzyme (Mae) mutant was not attenuated, and this independence of Mae and the role of PpdK was confirmed by the lack of attenuation of a double Mae-PckA mutant. Altogether, these results decouple fast growth rates from enhanced mouse lethality in the brucellae and suggest that an Fbp-GlpX-independent gluconeogenic mechanism is ancestral in this group and show differences in central C metabolic steps that may reflect a progressive adaptation to intracellular growth.
PubMed: 29675004
DOI: 10.3389/fmicb.2018.00641 -
Acta Crystallographica. Section F,... Jan 2022Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that...
Members of the bacterial genus Brucella cause brucellosis, a zoonotic disease that affects both livestock and wildlife. Brucella are category B infectious agents that can be aerosolized for biological warfare. As part of the structural genomics studies at the Seattle Structural Genomics Center for Infectious Disease (SSGCID), FolM alternative dihydrofolate reductases 1 from Brucella suis and Brucella canis were produced and their structures are reported. The enzymes share ∼95% sequence identity but have less than 33% sequence identity to other homologues with known structure. The structures are prototypical NADPH-dependent short-chain reductases that share their highest tertiary-structural similarity with protozoan pteridine reductases, which are being investigated for rational therapeutic development.
Topics: Brucella canis; Brucella suis; Brucellosis; Crystallography, X-Ray; Humans; Tetrahydrofolate Dehydrogenase
PubMed: 34981773
DOI: 10.1107/S2053230X21013078 -
Phenotypic and molecular identification of Brucella suis biotype 1 in a pig from Brazil-case report.Brazilian Journal of Microbiology :... Mar 2022Brucellosis is a zoonotic disease with a global impact. Brucella suis is one of the most pathogenic species to humans, requiring different measures for the control...
Brucellosis is a zoonotic disease with a global impact. Brucella suis is one of the most pathogenic species to humans, requiring different measures for the control and/or eradication of the disease. The serological investigation for brucellosis was performed in pigs, horses, dogs, and cattle on a farm with a history of abortion in sows and necropsy of a boar with severe necrosuppurative orchitis. One sow, two cows, and two dogs reveled positive to Rose Bengal Test (RBT), although only the sow had a confirmatory outcome in 2-mercaptoethanol (2-ME). The 2-ME-positive sow was euthanized and microbiological culture of lymph nodes and liver followed by biochemical characterization allowed phenotypic characterization of Brucella suis biotype 1. PCR multiplex Bruce-ladder and Suis-ladder enabled molecular confirmation, respectively, of Brucella suis and biotype 1. The transmission aspects of B. suis to pigs and other domestic species, the combination of diagnostic procedures to diagnosis, as well as human health concerns of brucellosis are discussed.
Topics: Animals; Brazil; Brucella suis; Brucellosis; Cattle; Dogs; Female; Horses; Humans; Male; Polymerase Chain Reaction; Pregnancy; Swine; Swine Diseases
PubMed: 34510396
DOI: 10.1007/s42770-021-00607-y -
Frontiers in Veterinary Science 2020Brucellosis is a highly contagious zoonosis caused by a species under the genus . A duplex recombinase polymerase amplification (Duplex RPA) assay for the specific...
Brucellosis is a highly contagious zoonosis caused by a species under the genus . A duplex recombinase polymerase amplification (Duplex RPA) assay for the specific detection of and was developed in this study. Primers were designed targeting hypothetical protein genes and membrane transporter genes of and , respectively. The newly developed assay was validated for its analytical sensitivity and specificity. Different samples were collected from the Qinghai, Inner Mongolia, and Xinjiang provinces. After DNA extraction, the samples were analyzed by Duplex RPA, real-time PCR, and multiplex AMOS PCR to estimate the prevalence of brucellosis in sheep and yak in West China. The analytical sensitivities of Duplex RPA were 9 × 10 plasmid copies of and 9 × 10 plasmid copies of , but by mixing the reaction tubes after 4 min of incubation, the sensitivities were 4 × 10 and 5 × 10 copies of and , respectively. There was no cross-reactivity with , and . The screening of field samples by Duplex RPA revealed that the prevalence of in sheep and yak was 75.8% and the prevalence of was 4.8%. Multiplex AMOS PCR showed that the prevalence of was 19.3%, and that of was 4.8%. It was concluded that the developed Duplex RPA is sensitive and specific to the detection of and differentiation between and which will be useful in epidemiological surveillance and in the clinical settings.
PubMed: 33330681
DOI: 10.3389/fvets.2020.539679 -
Microorganisms Jul 2020Brucellosis is one of the most important worldwide zoonoses of many countries including Egypt. Camel brucellosis has not gained much attention in Egypt yet. This study...
Brucellosis is one of the most important worldwide zoonoses of many countries including Egypt. Camel brucellosis has not gained much attention in Egypt yet. This study is focused on the three governorates with the highest camel populations and the largest camel markets in the country to determine the disease seroprevalence and identify the species in local camel holdings. In total, 381 serum samples were collected from male and female camels from Giza, Aswan, and Al-Bahr Al-Ahmar (the Red Sea) governorates. Samples were serologically examined using the Rose-Bengal plate test (RBPT), indirect ELISA (i-ELISA), competitive ELISA (c-ELISA) and complement fixation test (CFT). antibodies were detected in 59 (15.5%), 87 (22.8%), 77 (20.2%) and 118 (31.0%) of sera by RBPT, i-ELISA, c-ELISA and CFT, respectively. Using real-time PCR, DNA was amplified in 32 (8.4%) seropositive samples including (25/32), (5/32) and (2/32), defining a complex epidemiological status. To the best of our knowledge, this is the first study reporting DNA in camel serum. The risk-associated factors including age, sex, breed and geographical distribution were statistically analyzed, showing non-significant association with seroprevalence. The results of this study will raise awareness for camel brucellosis and help develop effective control strategies.
PubMed: 32668648
DOI: 10.3390/microorganisms8071035 -
Revue Scientifique Et Technique... Apr 2013Live attenuated brucellosis vaccines have been available for protecting domestic livestock against Brucella melitensis and B. abortus for more than 60 years. Current... (Review)
Review
Live attenuated brucellosis vaccines have been available for protecting domestic livestock against Brucella melitensis and B. abortus for more than 60 years. Current vaccines are effective in preventing abortion and transmission of brucellosis, but poor at preventing infection or seroconversion. In addition, they can induce abortions in pregnant animals and are infectious to humans. It can be argued that current vaccines were developed empirically in that the immunological mechanism(s) of action were not determined. Current knowledge suggests that both the innate and adaptive immune responses contribute to immunity against intracellular pathogens and that binding of pathogen structures onto pattern recognition receptors (PRRs) is crucial to the development of adaptive immunity. The phagosome appears to be vital for the presentation of antigens to T-cell subtypes that provide protective immunity to intracellular pathogens. The observation that killed bacteria or subunit vaccines do not appear to fully stimulate PRRs, or mimic Brucella trafficking through phagosomes, may explain their inability to induce immunity that equals the protection provided by live attenuated vaccines. Brucella appears to have multiple mechanisms that subvert innate and adaptive immunity and prevent or minimise immunological responses. New technologies, such as DNA vaccines and nanoparticles, may be capable of delivering Brucella antigens in a waythat induces protective immunity in domestic livestock or wildlife reservoirs of brucellosis. Because of the re-emergence of brucellosis worldwide, with an increasing incidence of human infection, there is a great need for improved brucellosis vaccines. The greatest need is for new or improved vaccines against B. melitensis and B. suis.
Topics: Adaptive Immunity; Animals; Animals, Wild; Brucella; Brucella Vaccine; Brucellosis; Humans; Immunization Schedule; Instinct; Livestock; Swine; Swine Diseases; Vaccination
PubMed: 23837378
DOI: 10.20506/rst.32.1.2201