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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 -
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 -
Frontiers in Cellular and Infection... 2023Globally, brucellosis is a widespread zoonotic disease. It is prevalent in more than 170 countries and regions. It mostly damages an animal's reproductive system and... (Review)
Review
Globally, brucellosis is a widespread zoonotic disease. It is prevalent in more than 170 countries and regions. It mostly damages an animal's reproductive system and causes extreme economic losses to the animal husbandry industry. Once inside cells, resides in a vacuole, designated the BCV, which interacts with components of the endocytic and secretory pathways to ensure bacterial survival. Numerous studies conducted recently have revealed that 's ability to cause a chronic infection depends on how it interacts with the host. This paper describes the immune system, apoptosis, and metabolic control of host cells as part of the mechanism of survival in host cells. contributes to both the body's non-specific and specific immunity during chronic infection, and it can aid in its survival by causing the body's immune system to become suppressed. In addition, regulates apoptosis to avoid being detected by the host immune system. The BvrR/BvrS, VjbR, BlxR, and BPE123 proteins enable to fine-tune its metabolism while also ensuring its survival and replication and improving its ability to adapt to the intracellular environment.
Topics: Animals; Brucella; Persistent Infection; Macrophages; Brucellosis; Vacuoles
PubMed: 37143745
DOI: 10.3389/fcimb.2023.1129172 -
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... 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 -
Revista Chilena de Infectologia :... Aug 2018
Topics: Anti-Bacterial Agents; Culture Media; Ochrobactrum anthropi
PubMed: 30534931
DOI: 10.4067/s0716-10182018000400431 -
Infection and Immunity May 2023Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types and/or . The genus Brucella has markedly... (Review)
Review
Brucella spp. are facultatively intracellular bacteria that can infect, survive, and multiply in various host cell types and/or . The genus Brucella has markedly expanded in recent years with the identification of novel species and hosts, which has revealed additional information about the cell and tissue tropism of these pathogens. Classically, Brucella spp. are considered to have tropism for organs that contain large populations of phagocytes such as lymph nodes, spleen, and liver, as well as for organs of the genital system, including the uterus, epididymis, testis, and placenta. However, experimental infections of several different cultured cell types indicate that Brucella may actually have a broader cell tropism than previously thought. Indeed, recent studies indicate that certain Brucella species in particular hosts may display a pantropic distribution . This review discusses the available knowledge on cell and tissue tropism of Brucella spp. in natural infections of various host species, as well as in experimental animal models and cultured cells.
Topics: Animals; Male; Female; Brucella; Phagocytes; Cell Line; Cells, Cultured; Tropism; Brucellosis
PubMed: 37129522
DOI: 10.1128/iai.00062-23