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Polish Journal of Microbiology Jun 2018Brucellae are Gram-negative, small rods infecting mammals and capable of causing disease called brucellosis. The infection results in abortion and sterility in domestic... (Review)
Review
Brucellae are Gram-negative, small rods infecting mammals and capable of causing disease called brucellosis. The infection results in abortion and sterility in domestic animals (sheeps, pigs, rams etc). Especially dangerous for humans are: Brucella melitensis, Brucella suis, Brucella abortus, and Brucella canis that trigger unspecific symptoms (flu-like manifestation). Brucella rods are introduced via host cells, by inhalation, skin abrasions, ingestion or mucosal membranes. The most important feature of Brucella is the ability to survive and multiply within both phagocytic and non-phagocytic cells. Brucella does not produce classical virulence factors: exotoxin, cytolisins, exoenzymes, plasmids, fimbria, and drug resistant forms. Major virulence factors are: lipopolysaccharide (LPS), T4SS secretion system and BvrR/BvrS system, which allow interaction with host cell surface, formation of an early, late BCV (Brucella Containing Vacuole) and interaction with endoplasmic reticulum (ER) when the bacteria multiply. The treatment of brucellosis is based on two-drug therapy, the most common combinations of antibiotics are: doxycycline with rifampicin or fluoroquinolones with rifampicin. Currently, also other methods are used to disrupt Brucella intracellular replication (tauroursodeoxycholic acid or ginseng saponin fraction A).
Topics: Animals; Anti-Bacterial Agents; Brucella; Brucellosis; Endoplasmic Reticulum; Host-Pathogen Interactions; Humans; Lipopolysaccharides; Macrophages; Sheep; Swine; Type IV Secretion Systems; Virulence Factors
PubMed: 30015453
DOI: 10.21307/pjm-2018-029 -
International Journal of Molecular... Oct 2020organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of... (Review)
Review
organisms are responsible for one of the most widespread bacterial zoonoses, named brucellosis. The disease affects several species of animals, including humans. One of the most intriguing aspects of the brucellae is that the various species show a ~97% similarity at the genome level. Still, the distinct species display different host preferences, zoonotic risk, and virulence. After 133 years of research, there are many aspects of the biology that remain poorly understood, such as host adaptation and virulence mechanisms. A strategy to understand these characteristics focuses on the relationship between the genomic diversity and host preference of the various species. Pseudogenization, genome reduction, single nucleotide polymorphism variation, number of tandem repeats, and mobile genetic elements are unveiled markers for host adaptation and virulence. Understanding the mechanisms of genome variability in the genus is relevant to comprehend the emergence of pathogens.
Topics: Animals; Brucella; Brucellosis; Evolution, Molecular; Genome, Bacterial; Genomics; Humans; Phylogeny; Polymorphism, Single Nucleotide; Virulence
PubMed: 33092044
DOI: 10.3390/ijms21207749 -
Microbiology and Molecular Biology... Feb 2021Bacteria in the genus are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where... (Review)
Review
Bacteria in the genus are important human and veterinary pathogens. The abortion and infertility they cause in food animals produce economic hardships in areas where the disease has not been controlled, and human brucellosis is one of the world's most common zoonoses. strains have also been isolated from wildlife, but we know much less about the pathobiology and epidemiology of these infections than we do about brucellosis in domestic animals. The brucellae maintain predominantly an intracellular lifestyle in their mammalian hosts, and their ability to subvert the host immune response and survive and replicate in macrophages and placental trophoblasts underlies their success as pathogens. We are just beginning to understand how these bacteria evolved from a progenitor alphaproteobacterium with an environmental niche and diverged to become highly host-adapted and host-specific pathogens. Two important virulence determinants played critical roles in this evolution: (i) a type IV secretion system that secretes effector molecules into the host cell cytoplasm that direct the intracellular trafficking of the brucellae and modulate host immune responses and (ii) a lipopolysaccharide moiety which poorly stimulates host inflammatory responses. This review highlights what we presently know about how these and other virulence determinants contribute to pathogenesis. Gaining a better understanding of how the brucellae produce disease will provide us with information that can be used to design better strategies for preventing brucellosis in animals and for preventing and treating this disease in humans.
Topics: Adaptation, Physiological; Animals; Bacterial Outer Membrane Proteins; Brucella; Brucellosis; Female; Host Specificity; Humans; Lipopolysaccharides; Macrophages; Pregnancy; Pregnancy Complications, Infectious; Trophoblasts; Type IV Secretion Systems; Virulence; Virulence Factors
PubMed: 33568459
DOI: 10.1128/MMBR.00021-19 -
The American Journal of Pathology Jun 2015This review of Brucella-host interactions and immunobiology discusses recent discoveries as the basis for pathogenesis-informed rationales to prevent or treat... (Review)
Review
This review of Brucella-host 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 system-dependent 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.
Topics: Animals; Brucella; Brucellosis; Host-Pathogen Interactions; Humans
PubMed: 25892682
DOI: 10.1016/j.ajpath.2015.03.003 -
Recent Patents on Anti-infective Drug... Apr 2013The genus Brucella is a member of family Brucellaceae and includes ten species which are small, non-motile, non-sporing, aerobic, gram-negative intracellular... (Review)
Review
The genus Brucella is a member of family Brucellaceae and includes ten species which are small, non-motile, non-sporing, aerobic, gram-negative intracellular coccobacilli. They are catalase, oxidase and urea positive bacteria. Members of the genus can grow on enriched media like blood agar or chocolate agar. Identification in species level can be done by agglutination with monospecific serum, cultivating the strains in the presence of dyes and/or with PCR methods. Antigenic structure of the Brucella is composed of surface, intracellular, and in vivo antigens. Thanks to various virulence factors that act as metabolic regulators, Brucella strains can protect themselves from immune system of the host, adapt easily to different environmental conditions, and multiply intracellular. Classification, epidemiological features, isolation and identification, antigenic structure and virulence factors of Brucella species along with the discussion of very few patents associated with Brucellosis have been reviewed in this paper.
Topics: Bacterial Typing Techniques; Brucella; Brucellosis; Ecosystem; Epitopes; Humans; Virulence Factors
PubMed: 22812617
DOI: No ID Found -
Critical Reviews in Microbiology Mar 2018The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic... (Review)
Review
The brucellae are facultative intracellular pathogens causing brucellosis, an important zoonosis. Here, we review the nutritional, genetic, proteomic and transcriptomic studies on Brucella carbon uptake and central metabolism, information that is needed for a better understanding of Brucella virulence. There is no uniform picture across species but the studies suggest primary and/or secondary transporters for unknown carbohydrates, lactate, glycerol phosphate, erythritol, xylose, ribose, glucose and glucose/galactose, and routes for their incorporation to central metabolism, including an erythritol pathway feeding the pentose phosphate cycle. Significantly, all brucellae lack phosphoenolpyruvate synthase and phosphofructokinase genes, which confirms previous evidence on glycolysis absence, but carry all Entner-Doudoroff (ED) pathway and Krebs cycle (and glyoxylate pathway) genes. However, glucose catabolism proceeds through the pentose phosphate cycle in the classical species, and the ED pathway operates in some rodent-associated brucellae, suggesting an ancestral character for this pathway in this group. Gluconeogenesis is functional but does not rely exclusively on classical fructose bisphosphatases. Evidence obtained using infection models is fragmentary but suggests the combined or sequential use of hexoses/pentoses, amino acids and gluconeogenic substrates. We also discuss the role of the phosphotransferase system, stringent reponse, quorum sensing, BvrR/S and sRNAs in metabolism control, an essential aspect of the life style of facultative intracellular parasites.
Topics: Brucella; Carbon; Gene Expression Regulation, Bacterial; Metabolic Networks and Pathways
PubMed: 28604247
DOI: 10.1080/1040841X.2017.1332002 -
Critical Reviews in Microbiology Aug 2016The brucellae are α-Proteobacteria causing brucellosis, an important zoonosis. Although multiplying in endoplasmic reticulum-derived vacuoles, they cause no cell death,... (Review)
Review
The brucellae are α-Proteobacteria causing brucellosis, an important zoonosis. Although multiplying in endoplasmic reticulum-derived vacuoles, they cause no cell death, suggesting subtle but efficient use of host resources. Brucellae are amino-acid prototrophs able to grow with ammonium or use glutamate as the sole carbon-nitrogen source in vitro. They contain more than twice amino acid/peptide/polyamine uptake genes than the amino-acid auxotroph Legionella pneumophila, which multiplies in a similar vacuole, suggesting a different nutritional strategy. During these two last decades, many mutants of key actors in nitrogen metabolism (transporters, enzymes, regulators, etc.) have been described to be essential for full virulence of brucellae. Here, we review the genomic and experimental data on Brucella nitrogen metabolism and its connection with virulence. An analysis of various aspects of this metabolism (transport, assimilation, biosynthesis, catabolism, respiration and regulation) has highlighted differences and similarities in nitrogen metabolism with other α-Proteobacteria. Together, these data suggest that, during their intracellular life cycle, the brucellae use various nitrogen sources for biosynthesis, catabolism and respiration following a strategy that requires prototrophy and a tight regulation of nitrogen use.
Topics: Animals; Brucella; Brucellosis; Host-Pathogen Interactions; Humans; Metabolic Networks and Pathways; Nitrogen; Virulence
PubMed: 25471320
DOI: 10.3109/1040841X.2014.962480 -
Veterinary Microbiology Dec 2002The genus Brucella contains alpha-Proteobacteria adapted to intracellular life within cells of a variety of mammals. Controversy has arisen concerning Brucella internal... (Review)
Review
The genus Brucella contains alpha-Proteobacteria adapted to intracellular life within cells of a variety of mammals. Controversy has arisen concerning Brucella internal taxonomy, and it has been proposed that the DNA-DNA hybridization-based genomospecies concept be applied to the genus. According to this view, only one species, Brucella melitensis, should be recognized, and the classical species should be considered as biovars (B. melitensis biovar melitensis; B. melitensis biovar abortus; etc.). However, a critical reappraisal of the species concept, a review of the population structure of bacteria and the analysis of Brucella genetic diversity by methods other than DNA-DNA hybridization show that there are no scientific grounds to apply the genomospecies concept to this genus. On the other hand, an enlarged biological species concept allows the definition of Brucella species that are consistent with molecular analyses and support the taxonomical standing of most classical species. Both the host range as a long-recognized biological criterion and the presence of species-specific markers in outer membrane protein genes and in other genes show that B. melitensis, B. abortus, B. ovis, B. canis and B. neotomae are not mere pathovars (or nomenspecies) but biologically meaningful species. The status of B. suis is, however, less clear. These approaches should be useful to define species for the marine mammal Brucella isolates, as illustrated by the grouping of the isolates from pinnipeds or from cetaceans by omp2 gene analysis. It is shown that a correct Brucella species definition is important to understand the evolution of the genus.
Topics: Biological Evolution; Brucella; Brucella melitensis; Classification; DNA, Bacterial; Phylogeny; Species Specificity
PubMed: 12414145
DOI: 10.1016/s0378-1135(02)00210-9 -
Critical Reviews in Microbiology 1990
Review
Topics: Animals; Brucella; Brucellosis; Cells, Cultured; Cloning, Molecular; DNA Transposable Elements; DNA, Bacterial; Disease Models, Animal; Genes, Bacterial; Mutation; Phagocytosis; Plasmids; Virulence
PubMed: 2154232
DOI: 10.3109/10408419009105726 -
Infection, Genetics and Evolution :... Aug 2021Remarkable genetic diversity and breadth of host species has been uncovered in the Brucella genus over the past decade, fundamentally changing our concept of what it... (Review)
Review
Remarkable genetic diversity and breadth of host species has been uncovered in the Brucella genus over the past decade, fundamentally changing our concept of what it means to be a Brucella. From ocean fishes and marine mammals, to pond dwelling amphibians, forest foxes, desert rodents, and cave-dwelling bats, Brucella have revealed a variety of previously unknown niches. Classical microbiological techniques have been able to help us classify many of these new strains but at times have limited our ability to see the true relationships among or within species. The closest relatives of Brucella are soil bacteria and the adaptations of Brucella spp. to live intracellularly suggest that the genus has evolved to live in vertebrate hosts. Several recently discovered species appear to have phenotypes that are intermediate between soil bacteria and core Brucella, suggesting that they may represent ancestral traits that were subsequently lost in the traditional species. Remarkably, the broad relationships among Brucella species using a variety of sequence and fragment-based approaches have been upheld when using comparative genomics with whole genomes. Nonetheless, genomes are required for fine-scale resolution of many of the relationships and for understanding the evolutionary history of the genus. We expect that the coming decades will reveal many more hosts and previously unknown diversity in a wide range of environments.
Topics: Animals; Biological Evolution; Brucella; Genetic Variation; Genome, Bacterial; Genomics; Phylogeny
PubMed: 33872784
DOI: 10.1016/j.meegid.2021.104865