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PLoS Neglected Tropical Diseases May 2020Brucellosis is a bacterial endemic zoonotic disease of global significance with detrimental impacts on public health and food animal production. It is caused by Brucella... (Review)
Review
Brucellosis is a bacterial endemic zoonotic disease of global significance with detrimental impacts on public health and food animal production. It is caused by Brucella spp., an expanding group of pathogens able to infect various host species. Bovines and small ruminants, which excrete the bacteria in milk and in reproductive discharges, are major sources of infection for humans and other animals. Contact with contaminated animals and consumption of unpasteurized dairy products are the main routes for human infection. In spite of the considerable progress of knowledge gained and success achieved in brucellosis control in the developed world, this disease continues to be an important burden in the Middle East (ME). Common risk factors implicated in the difficulty and complexity of brucellosis control within the region include (1) social and political instabilities; (2) insufficient resources and infrastructure for appropriate diagnosis, reporting, and implementation of control measures; (3) variation of livestock husbandry systems and their commingling with other livestock and wildlife; and (4) traditional cultural practices, including consumption of unpasteurized dairy products. Development of core interdisciplinary competencies is required for a true One Health-based endeavor against the disease. National awareness and educational programs addressing all population sectors from consumers to decision-makers seem to be the next logical, sustainable, and economically viable approach toward improving disease status in this region. In the present review, we describe the current situation of brucellosis in the ME, focusing on the major limitations and shortcomings regarding disease control. We propose a regional approach toward public awareness of brucellosis as the first step in mitigating the disease and discuss the potential benefits, and components of such a strategy, which can further be used as a model for other endemic zoonotic diseases.
Topics: Animals; Brucella; Brucellosis; Humans; Livestock; Middle East; One Health; Zoonoses
PubMed: 32437346
DOI: 10.1371/journal.pntd.0008071 -
BMC Microbiology Sep 2014Several intracellular bacterial pathogens have evolved subtle strategies to subvert vesicular trafficking pathways of their host cells to avoid killing and to replicate...
BACKGROUND
Several intracellular bacterial pathogens have evolved subtle strategies to subvert vesicular trafficking pathways of their host cells to avoid killing and to replicate inside the cells. Brucellae are Gram-negative facultative intracellular bacteria that are responsible for brucellosis, a worldwide extended chronic zoonosis. Following invasion, Brucella abortus is found in a vacuole that interacts first with various endosomal compartments and then with endoplasmic reticulum sub-compartments. Brucella establishes its replication niche in ER-derived vesicles. In the past, it has been proposed that B. abortus passed through the macroautophagy pathway before reaching its niche of replication. However, recent experiments provided evidence that the classical macroautophagy pathway was not involved in the intracellular trafficking and the replication of B. abortus in bone marrow-derived macrophages and in HeLa cells. In contrast, another study showed that macroautophagy favoured the survival and the replication of Brucella melitensis in infected RAW264.7 macrophages. This raises the possibility that B. abortus and B. melitensis followed different intracellular pathways before replicating. In the present work, we have addressed this issue by comparing the replication rate of B. abortus and B. melitensis in embryonic fibroblasts derived from wild-type and Atg5-/- mice, Atg5 being a core component of the canonical macroautophagic pathway.
RESULTS
Our results indicate that both B. abortus S2308 and B. melitensis 16M strains are able to invade and replicate in Atg5-deficient fibroblasts, suggesting that the canonical Atg5-dependent macroautophagic pathway is dispensable for Brucella replication. The number of viable bacteria was even slightly higher in Atg5-/- fibroblasts than in wild-type fibroblasts. This increase could be due to a more efficient uptake or to a better survival rate of bacteria before the beginning of the replication in Atg5-deficient cells as compared to wild-type cells. Moreover, our data show that the infection with B. abortus or with B. melitensis does not stimulate neither the conversion of LC3-I to LC3-II nor the membrane recruitment of LC3 onto the BCV.
CONCLUSION
Our study suggests that like Brucella abortus, Brucella melitensis does not subvert the canonical macroautophagy to reach its replicative niche or to stimulate its replication.
Topics: Animals; Autophagy; Autophagy-Related Protein 5; Brucella abortus; Brucella melitensis; Fibroblasts; Mice, Knockout; Microtubule-Associated Proteins
PubMed: 25179110
DOI: 10.1186/s12866-014-0223-5 -
PLoS Neglected Tropical Diseases Mar 2017Brucellosis is one of the most common zoonoses globally, and Central Asia remains a Brucella hotspot. The World Health Organization classifies brucellosis as a neglected...
Brucellosis is one of the most common zoonoses globally, and Central Asia remains a Brucella hotspot. The World Health Organization classifies brucellosis as a neglected zoonotic disease that is rarely in the spotlight for research and mainly affects poor, marginalized people. Urban and peri-urban farming is a common practice in many low-income countries, and it increases the incomes of families that are often restrained by limited economic resources. However, there is a concern that the growing number of people and livestock living close together in these areas will increase the transmission of zoonotic pathogens such as Brucella. This study investigates the presence of Brucella DNA in bovine milk in the urban and peri-urban area of Dushanbe, Tajikistan. Brucella DNA was detected in 10.3% of 564 cow milk samples by IS711-based real-time PCR. This finding is concerning because consumption of unpasteurized dairy products is common in the region. Furthermore, Brucella DNA was detected in the milk of all seropositive cows, but 8.3% of the seronegative cows also showed the presence of Brucella DNA. In addition, sequence analysis of the rpoB gene suggests that one cow was infected with B. abortus and another cow was most likely infected with B. melitensis. The discrepancies between the serology and real-time PCR results highlight the need to further investigate whether there is a need for implementing complementary diagnostic strategies to detect false serological negative individuals in Brucella surveillance, control, and eradication programmes. Furthermore, vaccination of cattle with S19 in addition to vaccination of small ruminants with Rev 1 might be needed in order to control Brucella infections in the livestock population but further research focusing on the isolation of Brucella is required to obtain a comprehensive understanding of the Brucella spp. circulating among the livestock in this region.
Topics: Agriculture; Animals; Brucella; Cattle; DNA, Bacterial; DNA-Directed RNA Polymerases; Humans; Milk; Prevalence; Real-Time Polymerase Chain Reaction; Sequence Analysis, DNA; Suburban Population; Tajikistan; Urban Population
PubMed: 28296882
DOI: 10.1371/journal.pntd.0005367 -
Recent Patents on Anti-infective Drug... Apr 2013In addition to natural climate variability observed over comparable time periods, climate change is attributed directly or indirectly to human activity, altering the... (Review)
Review
In addition to natural climate variability observed over comparable time periods, climate change is attributed directly or indirectly to human activity, altering the composition of global atmosphere. This phenomenon continues to be a significant and global threat for the humankind, and its impact compromises many aspects of the society at different levels, including health. The impact of climate change on zoonotic diseases has been largely ignored, particularly brucellosis. We here review some direct and indirect evidences of the impact of climate change and climate variability on brucellosis.
Topics: Animals; Brucella; Brucellosis; Brucellosis, Bovine; Cattle; Climate Change; Humans; South America; Zoonoses
PubMed: 22873353
DOI: 10.2174/1574891x11308010003 -
Croatian Medical Journal Aug 2010To describe and discuss the merits of various direct and indirect methods applied in vitro (mainly on blood or milk) or in vivo (allergic test) for the diagnosis of... (Review)
Review
AIM
To describe and discuss the merits of various direct and indirect methods applied in vitro (mainly on blood or milk) or in vivo (allergic test) for the diagnosis of brucellosis in animals.
METHODS
The recent literature on brucellosis diagnostic tests was reviewed. These diagnostic tests are applied with different goals, such as national screening, confirmatory diagnosis, certification, and international trade. The validation of such diagnostic tests is still an issue, particularly in wildlife. The choice of the testing strategy depends on the prevailing brucellosis epidemiological situation and the goal of testing.
RESULTS
Measuring the kinetics of antibody production after Brucella spp. infection is essential for analyzing serological results correctly and may help to predict abortion. Indirect ELISAs help to discriminate 1) between false positive serological reactions and true brucellosis and 2) between vaccination and infection. Biotyping of Brucella spp. provides valuable epidemiological information that allows tracing an infection back to the sources in instances where several biotypes of a given Brucella species are circulating. Polymerase chain reaction and new molecular methods are likely to be used as routine typing and fingerprinting methods in the coming years.
CONCLUSION
The diagnosis of brucellosis in livestock and wildlife is complex and serological results need to be carefully analyzed. The B. abortus S19 and B. melitensis Rev. 1 vaccines are the cornerstones of control programs in cattle and small ruminants, respectively. There is no vaccine available for pigs or for wildlife. In the absence of a human brucellosis vaccine, prevention of human brucellosis depends on the control of the disease in animals.
Topics: Animals; Animals, Wild; Bacterial Typing Techniques; Brucella; Brucellosis; Enzyme-Linked Immunosorbent Assay; Humans; Livestock; Mass Screening; Polymerase Chain Reaction; Public Health; Sensitivity and Specificity
PubMed: 20718082
DOI: 10.3325/cmj.2010.51.296 -
FEMS Microbiology Reviews May 2010There is currently no licensed vaccine for brucellosis in humans. Available animal vaccines may cause disease and are considered unsuitable for use in humans. However,... (Review)
Review
There is currently no licensed vaccine for brucellosis in humans. Available animal vaccines may cause disease and are considered unsuitable for use in humans. However, the causative pathogen, Brucella, is among the most common causes of laboratory-acquired infections and is a Center for Disease Control category B select agent. Thus, human vaccines for brucellosis are required. This review highlights the considerations that are needed in the journey to develop a human vaccine, including animal models, and includes an assessment of the current status of novel vaccine candidates.
Topics: Animals; Brucella; Brucella Vaccine; Brucellosis; Disease Models, Animal; Humans
PubMed: 20180858
DOI: 10.1111/j.1574-6976.2010.00211.x -
Microbes and Infection Dec 2013Brucella pathogens are responsible for brucellosis, a worldwide zoonosis. They are facultative intracellular pathogens characterized by their asymmetric division and... (Review)
Review
Brucella pathogens are responsible for brucellosis, a worldwide zoonosis. They are facultative intracellular pathogens characterized by their asymmetric division and their unipolar growth. This growth modality generates poles with specialized functions (through polar recruitment of polar adhesins or of cell cycle regulators) and progeny cells with potentially different fates.
Topics: Adhesins, Bacterial; Animals; Asymmetric Cell Division; Bacterial Proteins; Brucella; Brucellosis; Cell Cycle; DNA Repair; Flagella; Host-Pathogen Interactions; Humans
PubMed: 24141086
DOI: 10.1016/j.micinf.2013.10.008 -
Microbes and Infection Oct 2020Brucella infection is frequently acquired through the respiratory route. The pathogen disseminates systemically from the lungs to infect peripheral organs. In this... (Review)
Review
Brucella infection is frequently acquired through the respiratory route. The pathogen disseminates systemically from the lungs to infect peripheral organs. In this review we summarize the existing data on the pathogenesis of inhalational Brucella infection, the pulmonary immune response to the pathogen, and potential strategies for inducing protective lung immunity.
Topics: Animals; Brucella; Brucella Vaccine; Brucellosis; Humans; Immunity; Lung; Vaccination; Virulence
PubMed: 32535086
DOI: 10.1016/j.micinf.2020.06.001 -
Veterinary Research Mar 2022Brucella melitensis and Brucella ovis are gram-negative pathogens of sheep that cause severe economic losses and, although B. ovis is non-zoonotic, B. melitensis is the...
Brucella melitensis and Brucella ovis are gram-negative pathogens of sheep that cause severe economic losses and, although B. ovis is non-zoonotic, B. melitensis is the main cause of human brucellosis. B. melitensis carries a smooth (S) lipopolysaccharide (LPS) with an N-formyl-perosamine O-polysaccharide (O-PS) that is absent in the rough LPS of B. ovis. Their control and eradication require vaccination, but B. melitensis Rev 1, the only vaccine available, triggers anti-O-PS antibodies that interfere in the S-brucellae serodiagnosis. Since eradication and serological surveillance of the zoonotic species are priorities, Rev 1 is banned once B. melitensis is eradicated or where it never existed, hampering B. ovis control and eradication. To develop a B. ovis specific vaccine, we investigated three Brucella live vaccine candidates lacking N-formyl-perosamine O-PS: Bov::CAΔwadB (CO-independent B. ovis with truncated LPS core oligosaccharide); Rev1::wbdRΔwbkC (carrying N-acetylated O-PS); and H38ΔwbkF (B. melitensis rough mutant with intact LPS core). After confirming their attenuation and protection against B. ovis in mice, were tested in rams for efficacy. H38ΔwbkF yielded similar protection to Rev 1 against B. ovis but Bov::CAΔwadB and Rev1::wbdRΔwbkC conferred no or poor protection, respectively. All H38ΔwbkF vaccinated rams developed a protracted antibody response in ELISA and immunoprecipitation B. ovis diagnostic tests. In contrast, all remained negative in Rose Bengal and complement fixation tests used routinely for B. melitensis diagnosis, though some became positive in S-LPS ELISA owing to LPS core epitope reactivity. Thus, H38ΔwbkF is an interesting candidate for the immunoprophylaxis of B. ovis in B. melitensis-free areas.
Topics: Animals; Antibodies, Bacterial; Brucella Vaccine; Brucella melitensis; Brucella ovis; Brucellosis; Male; Mice; Sheep; Sheep Diseases
PubMed: 35236406
DOI: 10.1186/s13567-022-01034-z -
Journal of Bacteriology Aug 2014The brucellae are the etiological agents of brucellosis, a worldwide-distributed zoonosis. These bacteria are facultative intracellular parasites and thus are able to...
The brucellae are the etiological agents of brucellosis, a worldwide-distributed zoonosis. These bacteria are facultative intracellular parasites and thus are able to adjust their metabolism to the extra- and intracellular environments encountered during an infectious cycle. However, this aspect of Brucella biology is imperfectly understood, and the nutrients available in the intracellular niche are unknown. Here, we investigated the central pathways of C metabolism used by Brucella abortus by deleting the putative fructose-1,6-bisphosphatase (fbp and glpX), phosphoenolpyruvate carboxykinase (pckA), pyruvate phosphate dikinase (ppdK), and malic enzyme (mae) genes. In gluconeogenic but not in rich media, growth of ΔppdK and Δmae mutants was severely impaired and growth of the double Δfbp-ΔglpX mutant was reduced. In macrophages, only the ΔppdK and Δmae mutants showed reduced multiplication, and studies with the ΔppdK mutant confirmed that it reached the replicative niche. Similarly, only the ΔppdK and Δmae mutants were attenuated in mice, the former being cleared by week 10 and the latter persisting longer than 12 weeks. We also investigated the glyoxylate cycle. Although aceA (isocitrate lyase) promoter activity was enhanced in rich medium, aceA disruption had no effect in vitro or on multiplication in macrophages or mouse spleens. The results suggest that B. abortus grows intracellularly using a limited supply of 6-C (and 5-C) sugars that is compensated by glutamate and possibly other amino acids entering the Krebs cycle without a critical role of the glyoxylate shunt.
Topics: Animals; Brucella abortus; Brucellosis; Carbon; Disease Models, Animal; Fructose-Bisphosphatase; Gene Deletion; Malate Dehydrogenase; Metabolic Networks and Pathways; Mice; Pyruvate, Orthophosphate Dikinase; Virulence
PubMed: 24936050
DOI: 10.1128/JB.01663-14