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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 -
Clinical Microbiology Reviews Dec 2019The clinical presentation of brucellosis in humans is variable and unspecific, and thus, laboratory corroboration of the diagnosis is essential for the patient's proper... (Review)
Review
The clinical presentation of brucellosis in humans is variable and unspecific, and thus, laboratory corroboration of the diagnosis is essential for the patient's proper treatment. The diagnosis of brucellar infections can be made by culture, serological tests, and nucleic acid amplification assays. Modern automated blood culture systems enable detection of acute cases of brucellosis within the routine 5- to 7-day incubation protocol employed in clinical microbiology laboratories, although a longer incubation and performance of blind subcultures may be needed for protracted cases. Serological tests, though they lack specificity and provide results that may be difficult to interpret in individuals repeatedly exposed to organisms, nevertheless remain a diagnostic cornerstone in resource-poor countries. Nucleic acid amplification assays combine exquisite sensitivity, specificity, and safety and enable rapid diagnosis of the disease. However, long-term persistence of positive molecular test results in patients that have apparently fully recovered is common and has unclear clinical significance and therapeutic implications. Therefore, as long as there are no sufficiently validated commercial tests or studies that demonstrate an adequate interlaboratory reproducibility of the different homemade PCR assays, cultures and serological methods will remain the primary tools for the diagnosis and posttherapeutic follow-up of human brucellosis.
Topics: Brucella; Brucellosis; Clinical Laboratory Techniques; Humans; Molecular Diagnostic Techniques; Nucleic Acid Amplification Techniques; Serologic Tests
PubMed: 31722888
DOI: 10.1128/CMR.00073-19 -
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 -
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 -
International Journal of Molecular... Apr 2021Brucellosis is a highly prevalent zoonotic disease characterized by abortion and reproductive dysfunction in pregnant animals. Although the mortality rate of Brucellosis... (Review)
Review
Brucellosis is a highly prevalent zoonotic disease characterized by abortion and reproductive dysfunction in pregnant animals. Although the mortality rate of Brucellosis is low, it is harmful to human health, and also seriously affects the development of animal husbandry, tourism and international trade. Brucellosis is caused by , which is a facultative intracellular parasitic bacteria. It mainly forms -containing vacuoles (BCV) in the host cell to avoid the combination with lysosome (Lys), so as to avoid the elimination of it by the host immune system. not only has the ability to resist the phagocytic bactericidal effect, but also can make the host cells form a microenvironment which is conducive to its survival, reproduction and replication, and survive in the host cells for a long time, which eventually leads to the formation of chronic persistent infection. can proliferate and replicate in cells, evade host immune response and induce persistent infection, which are difficult problems in the treatment and prevention of Brucellosis. Therefore, the paper provides a preliminary overview of the facultative intracellular parasitic and immune escape mechanisms of , which provides a theoretical basis for the later study on the pathogenesis of .
Topics: Animals; Brucella; Brucellosis; Chronic Disease; Host-Pathogen Interactions; Humans
PubMed: 33916050
DOI: 10.3390/ijms22073673 -
Annual Review of Microbiology Sep 2023The cell envelope is a multilayered structure that insulates the interior of bacterial cells from an often chaotic outside world. Common features define the envelope... (Review)
Review
The cell envelope is a multilayered structure that insulates the interior of bacterial cells from an often chaotic outside world. Common features define the envelope across the bacterial kingdom, but the molecular mechanisms by which cells build and regulate this critical barrier are diverse and reflect the evolutionary histories of bacterial lineages. Intracellular pathogens of the genus exhibit marked differences in cell envelope structure, regulation, and biogenesis when compared to more commonly studied gram-negative bacteria and therefore provide an excellent comparative model for study of the gram-negative envelope. We review distinct features of the envelope, highlighting a conserved regulatory system that links cell cycle progression to envelope biogenesis and cell division. We further discuss recently discovered structural features of the envelope that ensure envelope integrity and that facilitate cell survival in the face of host immune stressors.
Topics: Cell Membrane; Cell Wall; Biological Evolution; Brucella; Cell Division
PubMed: 37104660
DOI: 10.1146/annurev-micro-032521-013159 -
International Journal of Molecular... Dec 2021Brucellosis is a highly prevalent zoonotic disease caused by . spp. are gram-negative facultative intracellular parasitic bacteria. Its intracellular survival and... (Review)
Review
Brucellosis is a highly prevalent zoonotic disease caused by . spp. are gram-negative facultative intracellular parasitic bacteria. Its intracellular survival and replication depend on a functional virB system, an operon encoded by VirB1-VirB12. Type IV secretion system (T4SS) encoded by the virB operon is an important virulence factor of . It can subvert cellular pathway and induce host immune response by secreting effectors, which promotes replication in host cells and induce persistent infection. Therefore, this paper summarizes the function and significance of the VirB system, focusing on the structure of the VirB system where VirB T4SS mediates biogenesis of the endoplasmic reticulum (ER)-derived replicative containing vacuole (rBCV), the effectors of T4SS and the cellular pathways it subverts, which will help better understand the pathogenic mechanism of and provide new ideas for clinical vaccine research and development.
Topics: Animals; Brucella; Brucellosis; Host-Pathogen Interactions; Humans; Operon; Type IV Secretion Systems; Virulence Factors
PubMed: 34948430
DOI: 10.3390/ijms222413637 -
Folia Microbiologica Feb 2020As dendritic cells (DCs) are among the first cells to encounter antigens, these cells trigger both innate and T cell responses, and are the most potent... (Review)
Review
As dendritic cells (DCs) are among the first cells to encounter antigens, these cells trigger both innate and T cell responses, and are the most potent antigen-presenting cells. Brucella spp., which is an intracellular facultative and stealthy pathogen, is able to evade the bactericidal activities of professional phagocytes. Several studies have demonstrated that Brucella can survive and replicate intracellularly, thereby provoking impaired maturation of DCs. Therefore, the interaction between DCs and Brucella becomes an interesting model to study the immune response. In this review, we first will describe the most common techniques for DCs differentiation in vitro as well as general features of brucellosis. Then, the interaction of DCs and Brucella, including pathogen recognition, molecular mechanisms of bacterial pathogenesis, and intracellular trafficking of Brucella to subvert innate response, will be reviewed. Finally, we will debate diversity in immunological DC response and the controversial role of DC activation against Brucella infection.
Topics: Animals; Brucella; Brucellosis; Cytoplasm; Dendritic Cells; Host-Pathogen Interactions; Humans; Mice
PubMed: 30783994
DOI: 10.1007/s12223-019-00691-6 -
Journal of Clinical Microbiology Aug 2023Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged...
Bacteria of the genus Brucella are facultative intracellular parasites that cause brucellosis, a severe animal and human disease. Recently, a group of taxonomists merged the brucellae with the primarily free-living, phylogenetically related spp. in the genus Brucella. This change, founded only on global genomic analysis and the fortuitous isolation of some opportunistic spp. from medically compromised patients, has been automatically included in culture collections and databases. We argue that clinical and environmental microbiologists should not accept this nomenclature, and we advise against its use because (i) it was presented without in-depth phylogenetic analyses and did not consider alternative taxonomic solutions; (ii) it was launched without the input of experts in brucellosis or ; (iii) it applies a non-consensus genus concept that disregards taxonomically relevant differences in structure, physiology, population structure, core-pangenome assemblies, genome structure, genomic traits, clinical features, treatment, prevention, diagnosis, genus description rules, and, above all, pathogenicity; and (iv) placing these two bacterial groups in the same genus creates risks for veterinarians, medical doctors, clinical laboratories, health authorities, and legislators who deal with brucellosis, a disease that is particularly relevant in low- and middle-income countries. Based on all this information, we urge microbiologists, bacterial collections, genomic databases, journals, and public health boards to keep the Brucella and genera separate to avoid further bewilderment and harm.
Topics: Ochrobactrum; Brucella; Terminology as Topic; Phylogeny; Brucellosis; Humans; Opportunistic Infections
PubMed: 37395662
DOI: 10.1128/jcm.00438-23