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Journal of Veterinary Science Aug 2017The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most... (Review)
Review
The search for ideal brucellosis vaccines remains active today. Currently, no licensed human or canine anti-brucellosis vaccines are available. In bovines, the most successful vaccine (S19) is only used in calves, as adult vaccination results in orchitis in male, prolonged infection, and possible abortion complications in pregnant female cattle. Another widely deployed vaccine (RB51) has a low protective efficacy. An ideal vaccine should exhibit a safe profile as well as enhance protective efficacy. However, currently available vaccines exhibit one or more major drawbacks. Smooth live attenuated vaccines suffer shortcomings such as residual virulence and serodiagnostic interference. Inactivated vaccines, in general, confer relatively low levels of protection. Recent developments to improve brucellosis vaccines include generation of knockout mutants by targeting genes involved in metabolism, virulence, and the lipopolysaccharide synthesis pathway, as well as generation of DNA vaccines, mucosal vaccines, and live vectored vaccines, have all produced varying degrees of success. Herein, we briefly review the bacteriology, pathogenesis, immunological implications, candidate vaccines, vaccinations, and models related to .
Topics: Animals; Brucella; Brucella Vaccine; Brucellosis; Cattle; Female; Humans; Male; Vaccines, Inactivated
PubMed: 28859268
DOI: 10.4142/jvs.2017.18.S1.281 -
PLoS Pathogens Jun 2022Brucellae are facultative intracellular Gram-negative coccobacilli that chronically infect various mammals and cause brucellosis. Human brucellosis is among the most...
Brucellae are facultative intracellular Gram-negative coccobacilli that chronically infect various mammals and cause brucellosis. Human brucellosis is among the most common bacterial zoonoses and the vast majority of cases are attributed to B. melitensis. Using transposon sequencing (Tn-seq) analysis, we showed that among 3369 predicted genes of the B. melitensis genome, 861 are required for optimal growth in rich medium and 186 additional genes appeared necessary for survival of B. melitensis in RAW 264.7 macrophages in vitro. As the mucosal immune system represents the first defense against Brucella infection, we investigated the early phase of pulmonary infection in mice. In situ analysis at the single cell level indicates a succession of killing and growth phases, followed by heterogenous proliferation of B. melitensis in alveolar macrophages during the first 48 hours of infection. Tn-seq analysis identified 94 additional genes that are required for survival in the lung at 48 hours post infection. Among them, 42 genes are common to RAW 264.7 macrophages and the lung conditions, including the T4SS and purine synthesis genes. But 52 genes are not identified in RAW 264.7 macrophages, including genes implicated in lipopolysaccharide (LPS) biosynthesis, methionine transport, tryptophan synthesis as well as fatty acid and carbohydrate metabolism. Interestingly, genes implicated in LPS synthesis and β oxidation of fatty acids are no longer required in Interleukin (IL)-17RA-/- mice and asthmatic mice, respectively. This demonstrates that the immune status determines which genes are required for optimal survival and growth of B. melitensis in vivo.
Topics: Administration, Intranasal; Animals; Brucella melitensis; Brucellosis; Lipopolysaccharides; Macrophages; Mammals; Mice
PubMed: 35771771
DOI: 10.1371/journal.ppat.1010621 -
Virulence Jan 2018
Topics: Brucella abortus; Brucellosis; Lipopolysaccharides; Virulence
PubMed: 29144201
DOI: 10.1080/21505594.2017.1395544 -
Clinical Microbiology and Infection :... Nov 2017
Topics: Animals; Brucella abortus; Brucella melitensis; Brucellosis; Cattle; Dogs; Goats; Humans; Sheep; Swine; Vietnam; Zoonoses
PubMed: 28669842
DOI: 10.1016/j.cmi.2017.06.028 -
Revista Chilena de Infectologia :... Apr 2015
Topics: Brucella canis
PubMed: 26065455
DOI: 10.4067/S0716-10182015000300011 -
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 -
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 -
Frontiers in Cellular and Infection... 2015Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular... (Review)
Review
Brucella spp. are intracellular bacterial pathogens that cause infection in domestic and wild animals. They are often used as model organisms to study intracellular bacterial infections. Brucella VirB T4SS is a key virulence factor that plays important roles in mediating intracellular survival and manipulating host immune response to infection. In this review, we discuss the roles of Brucella VirB T4SS and 15 effectors that are proposed to be crucial for Brucella pathogenesis. VirB T4SS regulates the inflammation response and manipulates vesicle trafficking inside host cells. VirB T4SS also plays crucial roles in the inhibition of the host immune response and intracellular survival during infection. Here, we list the key molecular events in the intracellular life cycle of Brucella that are potentially targeted by the VirB T4SS effectors. Elucidating the functions of these effectors will help clarify the molecular role of T4SS during infection. Furthermore, studying the effectors secreted by Brucella spp. might provide insights into the mechanisms used by the bacteria to hijack the host signaling pathways and aid in the development of better vaccines and therapies against brucellosis.
Topics: Animals; Brucella; Host-Pathogen Interactions; Humans; Protein Transport; Type IV Secretion Systems; Virulence Factors
PubMed: 26528442
DOI: 10.3389/fcimb.2015.00072 -
Journal of Molecular Biology Aug 2016Autophagy is a conserved lysosomal recycling process, which maintains cellular homeostasis during stress and starvation conditions by degrading and recycling proteins,... (Review)
Review
Autophagy is a conserved lysosomal recycling process, which maintains cellular homeostasis during stress and starvation conditions by degrading and recycling proteins, lipids, and carbohydrates, ultimately increasing nutrient availability in eukaryotes. An additional function of autophagy, termed xenophagy, is to detect, capture, and destroy invading microorganisms, such as viruses, bacteria, and protozoa, providing autophagy with a role in innate immunity. Many intracellular pathogens have, however, developed mechanisms to avoid xenophagy and have evolved strategies to take advantage of select autophagic processes to undergo their intracellular life cycle. This review article will discuss the molecular mechanisms used by the intracellular bacterial pathogens Francisella spp. and Brucella spp. to manipulate components of the autophagic pathway, promoting cytosolic growth in the case of Francisella spp. and facilitating cellular egress and cell-to-cell spread in the case of Brucella spp. These examples highlight how successful, highly infectious bacterial pathogens avoid or subvert host autophagy mechanisms normally employed to maintain eukaryotic homeostasis.
Topics: Animals; Autophagy; Brucella; Francisella; Host-Pathogen Interactions; Humans; Immune Evasion
PubMed: 27456933
DOI: 10.1016/j.jmb.2016.07.007 -
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