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Trends in Microbiology Dec 2015Brucellae are facultative intracellular pathogens. The recent development of methods and genetically engineered strains allowed the description of cell-cycle progression... (Review)
Review
Brucellae are facultative intracellular pathogens. The recent development of methods and genetically engineered strains allowed the description of cell-cycle progression of Brucella abortus, including unipolar growth and the ordered initiation of chromosomal replication. B. abortus cell-cycle progression is coordinated with intracellular trafficking in the endosomal compartments. Bacteria are first blocked at the G1 stage, growth and chromosome replication being resumed shortly before reaching the intracellular proliferation compartment. The control mechanisms of cell cycle are similar to those reported for the bacterium Caulobacter crescentus, and they are crucial for survival in the host cell. The development of single-cell analyses could also be applied to other bacterial pathogens to investigate their cell-cycle progression during infection.
Topics: Brucella abortus; Brucellosis; Caulobacter crescentus; Cell Cycle; Cell Line; Cell Proliferation; Chromosomes, Bacterial; DNA Replication; DNA, Bacterial; Endosomes; G1 Phase Cell Cycle Checkpoints; Host-Pathogen Interactions; Humans; Metabolic Networks and Pathways; Protein Transport
PubMed: 26497941
DOI: 10.1016/j.tim.2015.09.007 -
Frontiers in Cellular and Infection... 2012Since the first case of brucellosis detected in a dolphin aborted fetus, an increasing number of Brucella ceti isolates has been reported in members of the two suborders... (Review)
Review
Since the first case of brucellosis detected in a dolphin aborted fetus, an increasing number of Brucella ceti isolates has been reported in members of the two suborders of cetaceans: Mysticeti and Odontoceti. Serological surveys have shown that cetacean brucellosis may be distributed worldwide in the oceans. Although all B. ceti isolates have been included within the same species, three different groups have been recognized according to their preferred host, bacteriological properties, and distinct genetic traits: B. ceti dolphin type, B. ceti porpoise type, and B. ceti human type. It seems that B. ceti porpoise type is more closely related to B. ceti human isolates and B. pinnipedialis group, while B. ceti dolphin type seems ancestral to them. Based on comparative phylogenetic analysis, it is feasible that the B. ceti ancestor radiated in a terrestrial artiodactyl host close to the Raoellidae family about 58 million years ago. The more likely mode of transmission of B. ceti seems to be through sexual intercourse, maternal feeding, aborted fetuses, placental tissues, vertical transmission from mother to the fetus or through fish or helminth reservoirs. The B. ceti dolphin and porpoise types seem to display variable virulence in land animal models and low infectivity for humans. However, brucellosis in some dolphins and porpoises has been demonstrated to be a severe chronic disease, displaying significant clinical and pathological signs related to abortions, male infertility, neurobrucellosis, cardiopathies, bone and skin lesions, strandings, and death.
Topics: Animals; Brucella; Brucellosis; Cetacea; Fish Diseases; Genetic Variation; Genotype; Molecular Epidemiology; Phylogeny
PubMed: 22919595
DOI: 10.3389/fcimb.2012.00003 -
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 -
PloS One 2022Brucellae are intracellular sneaky bacteria and they can elude the host's defensive mechanisms, resulting in therapeutic failure. Therefore, the goal of this...
Brucellae are intracellular sneaky bacteria and they can elude the host's defensive mechanisms, resulting in therapeutic failure. Therefore, the goal of this investigation was to rapid identification of Brucella species collected from animals and humans in Saudi Arabia, as well as to evaluate their resistance to antibiotics. On selective media, 364 animal samples as well as 70 human blood samples were cultured. Serological and biochemical approaches were initially used to identify a total of 25 probable cultured isolates. The proteomics of Brucella species were identified using the MALDI Biotyper (MBT) system, which was subsequently verified using real-time polymerase chain reaction (real-time PCR) and microfluidic electrophoresis assays. Both Brucella melitensis (B. melitensis) and Brucella abortus (B. abortus) were tested for antimicrobial susceptibility using Kirby Bauer method and the E-test. In total, 25 samples were positive for Brucella and included 11 B. melitensis and 14 B. abortus isolates. Twenty-two out of 25 (88%) and 24/25 (96%) of Brucella strains were recognized through the Vitek 2 Compact system. While MBT was magnificently identified 100% of the strains at the species level with a score value more than or equal to 2.00. Trimethoprim-sulfamethoxazole, rifampin, ampicillin-sulbactam, and ampicillin resistance in B. melitensis was 36.36%, 31.82%, 27.27%, and 22.70%, respectively. Rifampin, trimethoprim-sulfamethoxazole, ampicillin, and ampicillin-sulbactam resistance was found in 35.71%, 32.14%, 32.14%, and 28.57% of B. abortus isolates, correspondingly. MBT confirmed by microfluidic electrophoresis is a successful approach for identifying Brucella species at the species level. The resistance of B. melitensis and B. abortus to various antibiotics should be investigated in future studies.
Topics: Animals; Anti-Bacterial Agents; Brucella; Brucellosis; Cattle; DNA, Bacterial; Drug Evaluation, Preclinical; Drug Resistance, Microbial; Genotype; Goats; Humans; Infection Control; Proteomics; Real-Time Polymerase Chain Reaction; Saudi Arabia
PubMed: 35025975
DOI: 10.1371/journal.pone.0262551 -
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 -
PLoS Neglected Tropical Diseases May 2020Brucellosis is a neglected zoonotic disease of remarkable importance worldwide. The focus of this systematic review was to investigate occupational brucellosis and to... (Meta-Analysis)
Meta-Analysis
Brucellosis is a neglected zoonotic disease of remarkable importance worldwide. The focus of this systematic review was to investigate occupational brucellosis and to identify the main infection risks for each group exposed to the pathogen. Seven databases were used to identify papers related to occupational brucellosis: CABI, Cochrane, Pubmed, Scielo, Science Direct, Scopus and Web of Science. The search resulted in 6123 studies, of which 63 were selected using the quality assessment tools guided from National Institutes of Health (NIH) and Case Report Guidelines (CARE). Five different job-related groups were considered greatly exposed to the disease: rural workers, abattoir workers, veterinarians and veterinary assistants, laboratory workers and hunters. The main risk factors and exposure sources involved in the occupational infection observed from the analysis of the articles were direct contact with animal fluids, failure to comply with the use of personal protective equipment, accidental exposure to live attenuated anti-brucellosis vaccines and non-compliance with biosafety standards. Brucella species frequently isolated from job-related infection were Brucella melitensis, Brucella abortus, Brucella suis and Brucella canis. In addition, a meta-analysis was performed using the case-control studies and demonstrated that animal breeders, laboratory workers and abattoir workers have 3.47 [95% confidence interval (CI); 1.47-8.19] times more chance to become infected with Brucella spp. than others individuals that have no contact with the possible sources of infection. This systematic review improved the understanding of the epidemiology of brucellosis as an occupational disease. Rural workers, abattoir workers, veterinarians, laboratory workers and hunters were the groups more exposed to occupational Brucella spp. infection. Moreover, it was observed that the lack of knowledge about brucellosis among frequently exposed professionals, in addition to some behaviors, such as negligence in the use of individual and collective protective measures, increases the probability of infection.
Topics: Abattoirs; Animals; Brucella; Brucellosis; Humans; Laboratory Personnel; Occupational Diseases; Occupational Exposure; Veterinarians
PubMed: 32392223
DOI: 10.1371/journal.pntd.0008164 -
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 -
Folia Microbiologica Oct 2020The evolutionary "success" of the genus Brucella depends on the ability to persist both in the environment as well as inside of even activated macrophages of the animal...
The evolutionary "success" of the genus Brucella depends on the ability to persist both in the environment as well as inside of even activated macrophages of the animal host. For that, the Brucellae produce catalase and superoxide dismutase to defend against oxidative stress. Since the deletion of the mglA gene in the B. abortus S19 vaccine strain resulted not only in an increased tolerance to HO but also in the induction of cytokines in macrophages, we here investigated the effect of oxidative stress (Fe and HO) on the survival of B. abortus S19 and the isogenic B. abortus S 19 ∆mglA 3.14 deletion mutant in comparison with B. neotomae 5K33, Brucella strain 83/13, and B. microti CCM4915. These Brucellae belong to different phylogenetic clades and show characteristic differences in the mgl-operon. From the various Brucellae tested, B. abortus S19 showed the highest susceptibility to oxidative stress and the lowest ability to survive inside of murine macrophages. B. abortus S19 ∆mglA 3.14 as well as B. neotomae, which also belongs to the classical core clade of Brucella and lacks the regulators of the mgl-operon, presented the highest degree of tolerance to HO but not in the survival in macrophages. The latter was most pronounced in case of an infection with B. 83/13 and B. microti CCM4915. The various Brucellae investigated here demonstrate significant differences in tolerance against oxidative stress and different survival in murine macrophages, which, however, do not correlate directly.
Topics: Adenosine Triphosphate; Animals; Brucella; Brucella abortus; Cell Line; Colony Count, Microbial; Cytokines; Genes, Bacterial; Hydrogen Peroxide; Iron; Macrophages; Mice; Microbial Viability; Mutation; Oxidative Stress; Species Specificity
PubMed: 32462327
DOI: 10.1007/s12223-020-00798-1 -
Veterinary Research Sep 2018Brucella bacteria cause brucellosis, a major zoonosis whose control requires efficient diagnosis and vaccines. Identification of classical Brucella spp. has...
Brucella bacteria cause brucellosis, a major zoonosis whose control requires efficient diagnosis and vaccines. Identification of classical Brucella spp. has traditionally relied on phenotypic characterization, including surface antigens and 5-10% CO necessity for growth (CO-dependence), a trait of Brucella ovis and most Brucella abortus biovars 1-4 strains. Although molecular tests are replacing phenotypic methods, CO-dependence remains of interest as it conditions isolation and propagation and reflects Brucella metabolism, an area of active research. Here, we investigated the connection of CO-dependence and carbonic anhydrases (CA), the enzymes catalyzing the hydration of CO to the bicarbonate used by anaplerotic and biosynthetic carboxylases. Based on the previous demonstration that B. suis carries two functional CAs (CAI and CAII), we analyzed the CA sequences of CO-dependent and -independent brucellae and spontaneous mutants. The comparisons strongly suggested that CAII is not functional in CO-dependent B. abortus and B. ovis, and that a modified CAII sequence explains the CO-independent phenotype of spontaneous mutants. Then, by mutagenesis and heterologous plasmid complementation and chromosomal insertion we proved that CAI alone is enough to support CO-independent growth of B. suis in rich media but not of B. abortus in rich media or B. suis in minimal media. Finally, we also found that insertion of a heterologous active CAII into B. ovis reverted the CO-dependence but did not alter its virulence in the mouse model. These results allow a better understanding of central aspects of Brucella metabolism and, in the case of B. ovis, provide tools for large-scale production of diagnostic antigens and vaccines.
Topics: Animals; Bacterial Proteins; Brucella abortus; Brucella ovis; Carbon Dioxide; Carbonic Anhydrases; Female; Mice; Mice, Inbred BALB C; Virulence
PubMed: 30185220
DOI: 10.1186/s13567-018-0583-1 -
Journal of Biomedicine & Biotechnology 2011Brucellosis is a chronic infectious disease caused by Brucella spp., a gram-negative facultative intracellular pathogen that affects humans and animals, leading to... (Review)
Review
Brucellosis is a chronic infectious disease caused by Brucella spp., a gram-negative facultative intracellular pathogen that affects humans and animals, leading to significant impact on public health and animal industry. Human brucellosis is considered the most prevalent bacterial zoonosis in the world and is characterized by fever, weight loss, depression, hepato/splenomegaly, osteoarticular, and genital infections. Relevant aspects of Brucella pathogenesis have been intensively investigated in culture cells and animal models. The mouse is the animal model more commonly used to study chronic infection caused by Brucella. This model is most frequently used to investigate specific pathogenic factors of Brucella spp., to characterize the host immune response, and to evaluate therapeutics and vaccines. Other animal species have been used as models for brucellosis including rats, guinea pigs, and monkeys. This paper discusses the murine and other laboratory animal models for human and animal brucellosis.
Topics: Animals; Brucella; Brucella Vaccine; Brucellosis; Disease Models, Animal; Guinea Pigs; Humans; Macaca mulatta; Mice; Rats
PubMed: 21403904
DOI: 10.1155/2011/518323