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PloS One 2020Brucellosis is a zoonotic disease known to be endemic to parts of western and sub-Saharan Africa. However, the epidemiology for humans and animals remains largely... (Review)
Review
Brucellosis is a zoonotic disease known to be endemic to parts of western and sub-Saharan Africa. However, the epidemiology for humans and animals remains largely unknown in many of these countries with Cameroon being a typical example. Despite common knowledge that brucellosis affects livestock, the actual number of infected animals remains unknown. Through a scoping review, the current known status of the disease is described. The aim is to ascertain relevant and publicly accessible research and knowledge of human and animal brucellosis in the country, and to provide an overview of the factors associated with its known persistence. Seroprevalence has been estimated and published in 12 separate instances (1 human; 9 cattle; 1 human and cattle; and 1 that includes cattle, pigs, and small ruminants), between 1982 and 2020, in 9 of the country's 10 geopolitical regions. In 1983, Brucella abortus and B. melitensis were isolated in cattle, but no further bacterial isolation has been published since. The seroprevalence from 196 total humans has ranged between 5.6% and 28.1%, and between 3.0% and 30.8% for 14,044 total cattle. As there is no ongoing surveillance program, it is not currently possible to identify the specific Brucella spp. that are endemic to the country and its regions. There are sufficient agricultural systems of cattle, pigs, goats, and sheep to sustain the presence of multiple Brucella spp. Surveillance information is the cornerstone of epidemiologic decision making, and is needed to direct policy makers, public health authorities, and veterinary services to appropriate actions. A combination of serological and molecular based diagnostics for surveillance is necessary to identify, quantify, and direct the appropriate public health interventions. Cameroon has an opportunity to build public and animal health infrastructure, leading the way for central Africa in the management and future eradication of brucellosis.
Topics: Animals; Brucella abortus; Brucella melitensis; Brucellosis; Cameroon; Endemic Diseases; Epidemiological Monitoring; Humans; Livestock; Seroepidemiologic Studies; Zoonoses
PubMed: 32986759
DOI: 10.1371/journal.pone.0239854 -
Pan-Proteomic Analysis and Elucidation of Protein Abundance among the Closely Related Species, and .Biomolecules May 2020Brucellosis is a zoonotic infection caused by bacteria of the genus . The species, and , major causative agents of human brucellosis, share remarkably similar genomes,...
Brucellosis is a zoonotic infection caused by bacteria of the genus . The species, and , major causative agents of human brucellosis, share remarkably similar genomes, but they differ in their natural hosts, phenotype, antigenic, immunogenic, proteomic and metabolomic properties. In the present study, label-free quantitative proteomic analysis was applied to investigate protein expression level differences. Type strains and field strains were each cultured six times, cells were harvested at a midlogarithmic growth phase and proteins were extracted. Following trypsin digestion, the peptides were desalted, separated by reverse-phase nanoLC, ionized using electrospray ionization and transferred into an linear trap quadrapole (LTQ) Orbitrap Velos mass spectrometer to record full scan MS spectra ( 300-1700) and tandem mass spectrometry (MS/MS) spectra of the 20 most intense ions. Database matching with the reference proteomes resulted in the identification of 826 proteins. The Cluster of Gene Ontologies of the identified proteins revealed differences in bimolecular transport and protein synthesis mechanisms between these two strains. Among several other proteins, antifreeze proteins, Omp10, superoxide dismutase and 30S ribosomal protein S14 were predicted as potential virulence factors among the proteins differentially expressed. All mass spectrometry data are available via ProteomeXchange with identifier PXD006348.
Topics: Bacterial Proteins; Brucella abortus; Brucella melitensis; Proteomics; Species Specificity
PubMed: 32486122
DOI: 10.3390/biom10060836 -
PLoS Neglected Tropical Diseases Sep 2022Brucellosis (Brucella melitensis) is endemic in many countries around the world, therefore, identifying what is required to control and prevent the disease is essential....
BACKGROUND
Brucellosis (Brucella melitensis) is endemic in many countries around the world, therefore, identifying what is required to control and prevent the disease is essential. The health promotion concept and five areas of action, presented in the Ottawa Charter (1986) may help understand how to go forward in the prevention of the disease. Israel serves as a case study.
AIM
To identify barriers to the control and prevention of brucellosis (Brucella melitensis) in Israel by analyzing trends in incidence in conjunction with interventions implemented over the last seven decades, applying the health promotion areas of action.
METHODS
1. A document review approach was adopted to develop a list of interventions implemented in Israel to prevent and control brucellosis and identify barriers to implementation. These were analysed using the health promotion areas of action. 2. Data from the mandatory reporting of infectious diseases in Israel regarding brucellosis in humans between 1951 and 2021 are presented and analyzed in conjunction with the interventions implemented.
RESULTS
A large range of interventions were implemented following outbreaks of the disease. These interventions followed the health promotion areas of action, including mainly: policy, education and environment and brought about a decrease in the disease among both animals and humans. However, major interventions were discontinued after a few years. In addition, we identified some areas of action that could be much improved on. The interventions, in many cases were not simultaneously implemented or coordinated, decreasing the chances of them having the expected long term impact.
CONCLUSIONS
Control and prevention of the disease in Israel is partial. Areas of action that could be improved include enforcement of regulations, strengthening community action and improving personal skills. Simultaneous and continuous implementation of the interventions may achieve the goals of sustained prevention and control. There seems to be a lack of a long-term strategy and an integrated holistic intervention approach that may contribute to the control and prevention of the disease.
Topics: Animals; Brucella melitensis; Brucellosis; Disease Outbreaks; Health Promotion; Humans; Israel
PubMed: 36155492
DOI: 10.1371/journal.pntd.0010816 -
BMC Veterinary Research Aug 2021UTP-glucose-1-phosphoryl transferase (UGPase) catalyzes the synthesis of UDP-glucose, which is essential for generating the glycogen needed for the synthesis of...
BACKGROUND
UTP-glucose-1-phosphoryl transferase (UGPase) catalyzes the synthesis of UDP-glucose, which is essential for generating the glycogen needed for the synthesis of bacterial lipopolysaccharide (LPS) and capsular polysaccharide, which play important roles in bacterial virulence. However, the molecular function of UGPase in Brucella is still unknown.
RESULTS
In this study, the ubiquitination modification of host immune-related protein in cells infected with UGPase-deleted or wild-type Brucella was analyzed using ubiquitination proteomics technology. The ubiquitination modification level and type of NF-κB Essential Modulator (NEMO or Ikbkg), a molecule necessary for NF-κB signal activation, was evaluated using Coimmunoprecipitation, Western blot, and dual-Luciferase Assay. We found 80 ubiquitin proteins were upregulated and 203 ubiquitin proteins were downregulated in cells infected with B. melitensis 16 M compared with those of B. melitensis UGPase-deleted strain (16 M-UGPase). Moreover, the ubiquitin-modified proteins were mostly enriched in the categories of regulation of kinase/NF-κB signaling and response to a bacterium, suggesting Brucella UGPase inhibits ubiquitin modification of related proteins in the host NF-κB signaling pathway. Further analysis showed that the ubiquitination levels of NEMO K63 (K63-Ub) and Met1 (Met1-Ub) were significantly increased in the 16 M-UGPase-infected cells compared with that of the 16 M-infected cells, further confirming that the ubiquitination levels of NF-κB signaling-related proteins were regulated by the bacterial UGPase. Besides, the expression level of IκBα was decreased, but the level of p-P65 was significantly increased in the 16 M-UGPase-infected cells compared with that of the 16 M- and mock-infected cells, demonstrating that B. melitensis UGPase can significantly inhibit the degradation of IκBα and the phosphorylation of p65, and thus suppressing the NF-κB pathway.
CONCLUSIONS
The results of this study showed that Brucella melitensis UGPase inhibits the activation of NF-κB by modulating the ubiquitination of NEMO, which will provide a new scientific basis for the study of immune mechanisms induced by Brucella.
Topics: Animals; Bacterial Proteins; Brucella melitensis; Brucellosis; Gene Expression Regulation; I-kappa B Kinase; Mice; NF-kappa B; RAW 264.7 Cells; Signal Transduction; UTP-Glucose-1-Phosphate Uridylyltransferase; Ubiquitin; Ubiquitination
PubMed: 34461896
DOI: 10.1186/s12917-021-02993-9 -
Archives of Razi Institute Feb 2022Brucellosis is one of the most important zoonotic diseases in many regions worldwide. This study aimed to investigate the antimicrobial properties of hydro-ethanolic...
Brucellosis is one of the most important zoonotic diseases in many regions worldwide. This study aimed to investigate the antimicrobial properties of hydro-ethanolic extracts of propolis (EEP) samples collected from six different regions of Iran against five () clinical isolates causing human brucellosis and an antibiotic-resistant vaccinal strain (RB51). clinical isolates were first carefully identified using conventional molecular typing and bio-typing methods. Different strains were then confronted with EEPs using the disk-diffusion agar method to evaluate the antimicrobial activity of each propolis extract. Chemical composition of EEPs was then determined using HPLC-DAD, and the main phenolic compounds were quantified. It was found that all EEPs displayed significant antimicrobial activities against strains, though to varying extents. All tested clinical strains were susceptible to different EEPs with inhibition zones ranging from 18 to 38 mm diameter. Interestingly, the RB51 vaccine strain was more susceptible to EEP6 (from Markazi province), compared to conventional antibiotics used in the treatment of brucellosis. Substantial differences observed in EEP antimicrobial activity could be due to their distinct botanical origins and chemical compositions as confirmed by our HPLC analysis. The promising inhibitory effect of some propolis preparations against a broad spectrum of strains points to the need for further studies in the context of systematic clinical investigations and opens up the way for the development of natural complements in support of conventional antibiotic therapy.
Topics: Anti-Bacterial Agents; Brucella melitensis; Brucellosis; Humans; Iran; Propolis
PubMed: 35891767
DOI: 10.22092/ari.2021.353395.1602 -
Archives of Razi Institute Mar 2021Brucellosis is recognized as a major public health concern leading to critical economic losses in livestock animals. The present study assessed Brucella spp. isolated...
Brucellosis is recognized as a major public health concern leading to critical economic losses in livestock animals. The present study assessed Brucella spp. isolated from aborted ovine and caprine fetuses in different parts of Iran between 2016 and 2019. It used classic and molecular methods in order to determine the Brucella species carrying higher risks of abortion complications in these animals. A total of 189 samples from 35 cases/case series from milk (16 sheep, and 8 goats), 19 abomasum content (sheep), and 146 aborted fetuses (116 sheep, and 30 goats) were bacteriologically examined. Subsequently, the resultant Brucella isolates were further characterized by phenotypic and molecular approaches. The multiplex Polymerase chain reaction (PCR) (Bruce-ladder) and IS711-based PCR were performed on all the extracted DNA to evaluate the presence of Brucella spp. As suggested by the obtained results, all recovered isolates from ovine and caprine abortion samples were either B. melitensis or B. abortus. An issue of concern was the implication of B. melitensis vaccine strain Rev1 in a small portion of sheep and goat abortion cases. Despite the recent B. abortus burden in ovine, aborted cases were predominantly associated with B. melitensis infections in both ovine and caprine, and B. melitensis biovar 1 was responsible for the majority of studied cases. These data and the techniques implemented in the present study can shed light on the level of implication of different Brucella species in ovine and caprine abortion in Iran. The present study identified Brucella agents responsible for abortion in small ruminants at the biovar level. Therefore, it provides precious information for future control programs and vaccination strategies in Middle Eastern regions.
Topics: Animals; Brucella abortus; Brucella melitensis; Brucellosis; Female; Goat Diseases; Goats; Pregnancy; Sheep; Sheep Diseases
PubMed: 33818957
DOI: 10.22092/ari.2019.128003.1398 -
Frontiers in Cellular and Infection... 2021, a notorious intracellular pathogen, causes chronic infections in many mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded...
, a notorious intracellular pathogen, causes chronic infections in many mammals, including humans. The twin-arginine translocation (Tat) pathway transports folded proteins across the cytoplasmic membrane; protein substrates translocated by include ABC transporters, oxidoreductases, and cell envelope biosynthesis proteins. Previously, we showed that a Tat mutant of M28 exhibits reduced survival within murine macrophages. In this study, we compared the host responses elicited by wild-type M28 and its Tat-mutant strains ex vivo. We utilized label-free quantitative proteomics to assess proteomic changes in RAW264.7 macrophages after infection with M28 and its Tat mutants. A total of 6085 macrophage proteins were identified with high confidence, and 79, 50, and 99 proteins were differentially produced upon infection with the Tat mutant at 4, 24, and 48 hpi, respectively, relative to the wild-type infection. Gene ontology and KEGG enrichment analysis indicated that immune response-related proteins were enriched among the upregulated proteins. Compared to the wild-type M28 infection, the most upregulated proteins upon Tat-mutant infection included the cytosolic nucleic acid signaling pathway-related proteins IFIH1, DHX58, IFI202, IFI204, and ISG15 and the NF-B signaling pathway-related proteins PTGS2, CD40, and TRAF1, suggesting that the host increases the production of these proteins in response to Tat mutant infection. Upregulation of some proteins was further verified by a parallel reaction monitoring (PRM) assay. ELISA and qRT-PCR assays indicated that Tat mutant infection significantly induced proinflammatory cytokine (TNF-α and IL-6) and nitric oxide (NO) production. Finally, we showed that the Tat mutant displays higher sensitivity to nitrosative stress than the wild type and that treatment with the NO synthase inhibitor L-NMMA significantly increases the intracellular survival of the Tat mutant, indicating that NO production contributes to restricting Tat mutant survival within macrophages. Collectively, this work improves our understanding of host immune responses to Tat mutants and provides insights into the mechanisms underlying the attenuated virulence of Tat mutants.
Topics: Animals; Arginine; Brucella melitensis; Brucellosis; Humans; Macrophages; Mice; Proteomics
PubMed: 34195100
DOI: 10.3389/fcimb.2021.679571 -
PLoS Neglected Tropical Diseases Aug 2017Caprine brucellosis is a chronic infectious disease caused by the gram-negative cocci-bacillus Brucella melitensis. Middle- to late-term abortion, stillbirths, and the... (Review)
Review
Caprine brucellosis is a chronic infectious disease caused by the gram-negative cocci-bacillus Brucella melitensis. Middle- to late-term abortion, stillbirths, and the delivery of weak offspring are the characteristic clinical signs of the disease that is associated with an extensive negative impact in a flock's productivity. B. melitensis is also the most virulent Brucella species for humans, responsible for a severely debilitating and disabling illness that results in high morbidity with intermittent fever, chills, sweats, weakness, myalgia, abortion, osteoarticular complications, endocarditis, depression, anorexia, and low mortality. Historical observations indicate that goats have been the hosts of B. melitensis for centuries; but around 1905, the Greek physician Themistokles Zammit was able to build the epidemiological link between "Malta fever" and the consumption of goat milk. While the disease has been successfully managed in most industrialized countries, it remains a significant burden on goat and human health in the Mediterranean region, the Middle East, Central and Southeast Asia (including India and China), sub-Saharan Africa, and certain areas in Latin America, where approximately 3.5 billion people live at risk. In this review, we describe a historical evolution of the disease, highlight the current worldwide distribution, and estimate (by simple formula) the approximate costs of brucellosis outbreaks to meat- and milk-producing farms and the economic losses associated with the disease in humans. Successful control leading to eradication of caprine brucellosis in the developing world will require a coordinated Global One Health approach involving active involvement of human and animal health efforts to enhance public health and improve livestock productivity.
Topics: Animals; Brucella melitensis; Brucellosis; Communicable Disease Control; Cost of Illness; Global Health; Goat Diseases; Goats; Humans; Neglected Diseases; Prevalence; Public Health; Zoonoses
PubMed: 28817647
DOI: 10.1371/journal.pntd.0005692 -
Journal of Infection in Developing... Jan 2023Brucellosis is an infectious disease caused by direct contact with infected animals or animal products contaminated with Brucella. Brucella is a Gram-negative aerobic...
INTRODUCTION
Brucellosis is an infectious disease caused by direct contact with infected animals or animal products contaminated with Brucella. Brucella is a Gram-negative aerobic coccobacillus that infects different types of animals and is considered to be an important zoonotic disease.
METHODOLOGY
Brucella were isolated from blood samples and identified following biochemical tests and agglutination with A and M monospecific antisera. Furthermore, Brucella antibody titers of the tested sera were obtained by the microtiter agglutination method (MAM).
RESULTS
The main Brucella species isolated in Oman was B. melitensis. However, in countries bordering Oman and their neighboring countries, both B. melitensis and B. abortus have been isolated and identified. A total of 412 human patients with suspected cases of brucellosis were admitted to the Department of Communicable Disease Surveillance and Control in the Dhofar Governorate for diagnosis and treatment. During the year 2015, a total of 343 human cases were positively diagnosed with brucellosis in the Dhofar Governorate. During the years 2015 to 2019, a total of 10,492 animals were examined in different Governorates of Oman for brucellosis. The results indicated that 1161 (11%) animals were serologically positive for brucellosis.
CONCLUSIONS
The results of this study confirmed that Brucella melitensis is the main species responsible for human brucellosis in Oman. It was not surprising that the Dhofar Governorate exhibited a high percentage of infected patients since it is culturally acceptable to drink raw camel milk (unpasteurized), unlike cow milk which is pasteurized.
Topics: Animals; Female; Cattle; Humans; Oman; Brucellosis; Brucella melitensis; Epidemiologic Studies; Serum
PubMed: 36795918
DOI: 10.3855/jidc.17286 -
Frontiers in Immunology 2022Re-emerging zoonotic pathogen spp. continues to impact developing countries and persists in expanding populations of wildlife species in the US, constantly threatening...
Re-emerging zoonotic pathogen spp. continues to impact developing countries and persists in expanding populations of wildlife species in the US, constantly threatening infection of our domestic herds. The development of improved animal and human vaccines remains a priority. In this study, immunity to a novel live attenuated strain, termed znBM-mC, was characterized. An oral prime, intranasal (IN) boost strategy conferred exquisite protection against pulmonary challenge, with wild-type (wt) providing nearly complete protection in the lungs and spleens from brucellae colonization. Vaccination with znBM-mC showed an IFN-γ CD8 T-cell bias in the lungs as opposed to Rev 1-vaccinated mice showing IFN-γ CD4 T-cell inclination. Lung CD4 and CD8 effector memory T cells (TEMs) increased over 200-fold; and lung CD4 and CD8 resident memory T cells (TRMs) increased more than 250- and 150-fold, respectively. These T cells served as the primary producers of IFN-γ in the lungs, which was essential for vaccine clearance and the predominant cytokine generated pre-and post-challenge with wt 16M; znBM-mC growth could not be arrested in IFN-γ mice. Increases in lung TNF-α and IL-17 were also induced, with IL-17 being mostly derived from CD4 T cells. Vaccination of CD4, CD8, and B6 mice with znBM-mC conferred full protection in the lungs and spleens post-pulmonary challenge with virulent vaccination of IL-17 mice resulted in the protection of the lungs, but not the spleen. These data demonstrate the efficacy of mucosal vaccine administration for the generation of protective memory T cells against wt .
Topics: Humans; Mice; Animals; Brucella melitensis; Brucella Vaccine; Interleukin-17; Brucellosis; Tumor Necrosis Factor-alpha; Vaccination; CD8-Positive T-Lymphocytes; T-Lymphocyte Subsets; CD4-Positive T-Lymphocytes
PubMed: 36263034
DOI: 10.3389/fimmu.2022.995327