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FEMS Microbiology Letters Feb 2004Pathogenicity islands, specialized secretion systems, virulence plasmids, fimbriae, pili, adhesins, and toxins are all classical bacterial virulence factors. However,... (Review)
Review
Pathogenicity islands, specialized secretion systems, virulence plasmids, fimbriae, pili, adhesins, and toxins are all classical bacterial virulence factors. However, many of these factors, though widespread among bacterial pathogens, are not necessarily found among bacteria that colonize eukaryotic cells in a pathogenic/symbiotic relationship. Bacteria that form these relationships have developed other strategies to infect and grow in their hosts. This is particularly true for Brucella and other members of the class Proteobacteria. Thus far the identification of virulence factors for Brucella has been largely dependent on large-scale screens and testing in model systems. The genomes of the facultative intracellular pathogens Brucella melitensis and Brucella suis were sequenced recently. This has identified several more potential virulence factors for Brucella that were not found in large screens. Here, we present an overall view of Brucella virulence by compiling virulence data from the study of 184 attenuated mutants.
Topics: Animals; Brucella; Genome, Bacterial; Humans; Models, Genetic; Virulence
PubMed: 14979322
DOI: 10.1016/S0378-1097(03)00963-7 -
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 -
Veterinary Microbiology May 2008The first species of Brucella was isolated and characterized almost 120 years ago and recently the complete nucleotide sequences of the genomes of a number of... (Review)
Review
The first species of Brucella was isolated and characterized almost 120 years ago and recently the complete nucleotide sequences of the genomes of a number of well-characterized Brucella strains have been determined. However, compared to other bacterial pathogens relatively little is known about the factors contributing to its persistence in the host and multiplication within phagocytic cells. Also, many aspects of interaction between Brucella and their host remain unclear. Molecular characterization of intracellular survival process of Brucella is important as it will provide guidance for prevention and control. One of the features that distinguish Brucella is that they do not express classical virulence factors. Thus identification of virulence factors has been elusive and some of the identifications are putative. Disruption of putative virulence genes and studying their effect on attenuation in cell lines or mouse models is a widely used method. However, in most cases it is not apparent whether the mutated genes encode virulence factors or merely affect metabolic pathways of the pathogen. In addition, some mutations in Brucella can be compensated by redundancy or backup mechanisms. This review will examine known virulence genes (real and putative) identified to date and the mechanisms that contribute to the intracellular survival of Brucella and its ability to establish chronic infection.
Topics: Brucella; Virulence; Virulence Factors
PubMed: 18226477
DOI: 10.1016/j.vetmic.2007.11.023 -
Veterinary Pathology Nov 2014Fifty years ago, bacteria in the genus Brucella were known to cause infertility and reproductive losses. At that time, the genus was considered to contain only 3... (Review)
Review
Fifty years ago, bacteria in the genus Brucella were known to cause infertility and reproductive losses. At that time, the genus was considered to contain only 3 species: Brucella abortus, Brucella melitensis, and Brucella suis. Since the early 1960s, at least 7 new species have been identified as belonging to the Brucella genus (Brucella canis, Brucella ceti, Brucella inopinata, Brucella microti, Brucella neotomae, Brucella ovis, and Brucella pinnipedialis) with several additional new species under consideration for inclusion. Although molecular studies have found such high homology that some authors have proposed that all Brucella are actually 1 species, the epidemiologic and diagnostic benefits for separating the genus based on phenotypic characteristics are more compelling. Although pathogenic Brucella spp have preferred reservoir hosts, their ability to infect numerous mammalian hosts has been increasingly documented. The maintenance of infection in new reservoir hosts, such as wildlife, has become an issue for both public health and animal health regulatory personnel. Since the 1960s, new information on how Brucella enters host cells and modifies their intracellular environment has been gained. Although the pathogenesis and histologic lesions of B. abortus, B. melitensis, and B. suis in their preferred hosts have not changed, additional knowledge on the pathology of these brucellae in new hosts, or of new species of Brucella in their preferred hosts, has been obtained. To this day, brucellosis remains a significant human zoonosis that is emerging or reemerging in many parts of the world.
Topics: Animals; Animals, Wild; Brucella; Brucella Vaccine; Brucellosis; Communicable Diseases, Emerging; Disease Models, Animal; Disease Reservoirs; Humans; Zoonoses
PubMed: 24981716
DOI: 10.1177/0300985814540545 -
Briefings in Functional Genomics Nov 2011The genus Brucella includes species considered among the worlds most important zoonotic pathogens, with brucellosis remaining a significant problem in large parts of the... (Review)
Review
The genus Brucella includes species considered among the worlds most important zoonotic pathogens, with brucellosis remaining a significant problem in large parts of the world. Over the last decade a number of Brucella genomes have been fully sequenced providing new insights into this relatively poorly understood group of organisms. In the forthcoming months and years, the availability of many additional genomes should help in further understanding of the evolution, host specificity and pathogenicity of this group as well as providing a resource to further improve epidemiological typing tools. This article describes progress to date and looks forward to the opportunities that should be afforded as we enter an era of multiple, freely available, Brucella genome sequences.
Topics: Animals; Brucella; Genome, Bacterial; Genomics; Humans; Phylogeny; Sequence Analysis; Species Specificity
PubMed: 21930657
DOI: 10.1093/bfgp/elr026 -
FEBS Letters Oct 2011"In vivo" bacterial nutrition, i.e. the nature of the metabolic network and substrate(s) used by bacteria within their host, is a fundamental aspect of pathogenic or... (Review)
Review
"In vivo" bacterial nutrition, i.e. the nature of the metabolic network and substrate(s) used by bacteria within their host, is a fundamental aspect of pathogenic or symbiotic lifestyles. A typical example are the Brucella spp., facultative intracellular pathogens responsible for chronic infections of animals and humans. Their virulence relies on their ability to modulate immune response and the physiology of host cells, but the fine-tuning of their metabolism in the host during infection appears increasingly crucial. Here we review new insights on the links between Brucella virulence and metabolism, pointing out the need to investigate both aspects to decipher Brucella infectious strategies.
Topics: Adaptation, Physiological; Animals; Brucella; Brucellosis; Humans; Mutation; Quorum Sensing; Virulence
PubMed: 21864534
DOI: 10.1016/j.febslet.2011.08.011 -
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 -
Annual Review of Microbiology 2003The capacity of the Brucella spp. to establish and maintain long-term residence in the phagosomal compartment of host macrophages is critical to their ability to produce... (Review)
Review
The capacity of the Brucella spp. to establish and maintain long-term residence in the phagosomal compartment of host macrophages is critical to their ability to produce chronic infections in their mammalian hosts. The RNA binding protein host factor I (HF-I) encoded by the hfq gene is required for the efficient translation of the stationary-phase sigma factor RpoS in many bacteria, and a Brucella abortus hfq mutant displays a phenotype in vitro, which suggests that it has a generalized defect in stationary-phase physiology. The inability of the B. abortus hfq mutant to survive and replicate in a wild-type manner in cultured murine macrophages, and the profound attenuation displayed by this strain and its B. melitensis counterpart in experimentally infected animals indicate that stationary-phase physiology plays an essential role in the capacity of the brucellae to establish and maintain long-term intracellular residence in host macrophages. The nature of the Brucella HF-I-regulated genes that have been identified to date suggests that the corresponding gene products contribute to the remarkable capacity of the brucellae to resist the harsh environmental conditions they encounter during their prolonged residence in the phagosomal compartment.
Topics: Animals; Brucella; Brucellosis; Gene Expression Regulation, Bacterial; Genome, Bacterial; Host Factor 1 Protein; Humans; Phagosomes; Virulence
PubMed: 12730323
DOI: 10.1146/annurev.micro.57.030502.090803 -
Veterinary Microbiology Dec 2002Brucella organisms are pathogens that ultimate goal is to propagate in their preferred niche, the cell. Upon cell contact the bacteria is internalized via receptor... (Review)
Review
Brucella organisms are pathogens that ultimate goal is to propagate in their preferred niche, the cell. Upon cell contact the bacteria is internalized via receptor molecules by activating small GTPases of the Rho subfamily and by a moderate recruitment of actin filaments. Once inside cells, Brucella localizes in early phagosomes, where it avoids fusion with late endosomes and lysosomes. These early events require the control of Rab small GTPases, and cytokines such as the G-CSF. Then, the bacterium redirects its trafficking to autophagosomes and finally reaches the endoplasmic reticulum, where it extensively replicates. Some of the bacterial molecular determinants involved in the internalization and early events after ingestion are controlled by the BvrS/BvrR two component regulatory system, whereas the intracellular trafficking beyond this early compartments are controlled by the VirB type IV secretion system. Once inside the endoplasmic reticulum, Brucella extensively replicates without restricting basic cellular functions or inducing obvious damage to cells. The integrity of Brucella LPS on the bacterial surface is one of the required factors for Brucella intracellular survival, and therefore for virulence.
Topics: Animals; Brucella; Cell Division; Granulocyte Colony-Stimulating Factor; Intracellular Fluid; Macrophages; Mucous Membrane; Phagocytosis; rab GTP-Binding Proteins
PubMed: 12414149
DOI: 10.1016/s0378-1135(02)00214-6 -
Journal of Infection in Developing... Jul 2015Brucellosis is a zoonotic and contagious infectious disease caused by infection with Brucella species. The infecting brucellae are capable of causing a devastating... (Review)
Review
Brucellosis is a zoonotic and contagious infectious disease caused by infection with Brucella species. The infecting brucellae are capable of causing a devastating multi-organ disease in humans with serious health complications. The pathogenesis of Brucella infection is influenced largely by host factors, Brucella species/strain, and the ability of invading brucellae to survive and replicate within mononuclear phagocytic cells, preferentially macrophages (Mf). Consequently, the course of human infection may appear as an acute fatal or progress into chronic debilitating infection with periodical episodes that leads to bacteremia and death. The existence of brucellae inside Mf represents one of the strategies used by Brucella to evade the host immune response and is responsible for treatment failure in certain human populations treated with anti-Brucella drugs. Moreover, the persistence of brucellae inside Mf complicates the diagnosis and may affect the host cell signaling pathways with consequent alterations in both innate and adaptive immune responses. Therefore, there is an urgent need to pursue the development of novel drugs and/or vaccine targets against human brucellosis using high throughput technologies in genomics, proteomics, and immunology.
Topics: Brucella; Brucellosis; Host-Pathogen Interactions; Humans; Macrophages
PubMed: 26230118
DOI: 10.3855/jidc.6625