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autophagy favors brucella melitensis survival in infected macrophages.this study investigated the role of autophagy in the survival of the invasive bacterium brucella melitensis strain 16m in murine macrophages. here, brucella melitensis 16m was found to trigger autophagosome formation, enhance autophagy flux and increase the expression level of the autophagy marker protein lc3-ii. when autophagy was pharmacologically inhibited by 3-methyladenine (3-ma), brucella replication efficiency was significantly decreased (p < 0.05). these results suggest that autophagy fa ...201222367856
vaccination programs for reproductive disorders of small ruminants.vaccines are available for the control of contagious epididymitis and abortion in small ruminants, although many of them have significant limitations either in efficacy or safety to both the animals vaccinated and to the people handling the vaccine or animals. shelf-life of vaccines should be extended and improved, so that the vaccine remains effective with longer term storage and ideally without refrigeration, so that use in under-developed rural areas is not restricted (e.g., brucella melitens ...201222364910
deep sequencing-based expression transcriptional profiling changes during brucella infection.brucellosis is a worldwide zoonotic infectious disease that has significant economic effects on animal production and human health. the host macrophage -brucella interaction is critical to the establishment of infections. thus, the kinetic transcriptional profile of gene expression in macrophages infected with the brucella melitensis strain 16m was investigated in the current study using a technology based on deep sequencing. the total rna was extracted from macrophages 0, 4, and 24 h post-infec ...201222342430
efficacy evaluation of live escherichia coli expression brucella p39 protein combined with cpg oligodeoxynucleotides vaccine against brucella melitensis 16m, in balb/c mice.brucella is gram-negative bacteria responsible for brucellosis in a wide variety of animals and humans. balb/c mice were immunized with live escherichia coli expression the p39 gene of brucella melitensis, a gene coding for the periplasmic binding protein. mice were injected with either e. coli bl21 (de3) pet15b or e. coli bl21 (de3) pet15b-p39 alone or adjuvanted with either cpg oligodeoxynucleotides (cpg odn) or non-cpg odn. e. coli bl21 (de3) pet15b-p39 with cpg odn or with non-cpg odn mice g ...201222296786
cross-border molecular tracing of brucellosis in europe.to assess the general impact of endemic countries on the re-emergence of brucellosis in non-endemic regions of the european union, the genetic fingerprints of brucella melitensis strains imported to germany were compared to ovine strains from turkey in a molecular epidemiological study. genotyping of 66 brucella strains (based on multiple locus of variable number of tandem repeats analysis) isolated from german travellers and turkish immigrants living in germany revealed epidemiological concorda ...201222277829
brucella endocarditis in prosthetic valves.none declared.201224493988
16s rrna and omp31 gene based molecular characterization of field strains of b. melitensis from aborted foetus of goats in india.brucellosis is a reemerging infectious zoonotic disease of worldwide importance. in human, it is mainly caused by brucella melitensis, a natural pathogen for goats. in india, a large number of goats are reared in semi-intensive to intensive system within the close vicinity of human being. at present, there is no vaccination and control strategy for caprine brucellosis in the country. thus, to formulate an effective control strategy, the status of etiological agent is essential. to cope up with t ...201324453799
systems biology analysis of brucella infected peyer's patch reveals rapid invasion with modest transient perturbations of the host transcriptome.brucella melitensis causes the most severe and acute symptoms of all brucella species in human beings and infects hosts primarily through the oral route. the epithelium covering domed villi of jejunal-ileal peyer's patches is an important site of entry for several pathogens, including brucella. here, we use the calf ligated ileal loop model to study temporal in vivo brucella-infected host molecular and morphological responses. our results document brucella bacteremia occurring within 30 min afte ...201324349118
mlva genotyping of brucella melitensis and brucella abortus isolates from different animal species and humans and identification of brucella suis vaccine strain s2 from cattle in china.in china, brucellosis is an endemic disease and the main sources of brucellosis in animals and humans are infected sheep, cattle and swine. brucella melitensis (biovars 1 and 3) is the predominant species, associated with sporadic cases and outbreak in humans. isolates of b. abortus, primarily biovars 1 and 3, and b. suis biovars 1 and 3 are also associated with sporadic human brucellosis. in this study, the genetic profiles of b. melitensis and b. abortus isolates from humans and animals were a ...201324124546
a literature review of laboratory-acquired brucellosis.brucellosis is a bacterial zoonotic disease which has been associated with laboratory-acquired infections. no recent reviews have addressed the characteristics of laboratory-acquired brucellosis (lab). english-language literature was reviewed to identify reports of laboratory exposures to brucella spp. and lab cases between 1982 and 2007. evaluation of 28 case reports identified 167 potentially exposed laboratory workers, of whom 71 had lab. nine reports were identified that summarized an additi ...201323824774
impact of hfq on global gene expression and intracellular survival in brucella melitensis.brucella melitensis is a facultative intracellular bacterium that replicates within macrophages. the ability of brucellae to survive and multiply in the hostile environment of host macrophages is essential to its virulence. the rna-binding protein hfq is a global regulator that is involved in stress resistance and pathogenicity. here we demonstrate that hfq is essential for stress adaptation and intracellular survival in b. melitensis. a b. melitensis hfq deletion mutant exhibits reduced surviva ...201323977181
comparative genomic analysis of brucella melitensis vaccine strain m5 provides insights into virulence attenuation.the brucella melitensis vaccine strain m5 is widely used to prevent and control brucellosis in animals. in this study, we determined the whole-genome sequence of m5, and conducted a comprehensive comparative analysis against the whole-genome sequence of the virulent strain 16 m and other reference strains. this analysis revealed 11 regions of deletion (rds) and 2 regions of insertion (ris) within the m5 genome. among these regions, the sequences encompassed in 5 rds and 1 ri showed consistent va ...201323967122
rapid quantitative detection of brucella melitensis by a label-free impedance immunosensor based on a gold nanoparticle-modified screen-printed carbon electrode.a rapid and simple method for quantitative monitoring of brucella melitensis using electrochemical impedance spectroscopy (eis) is reported for the first time. the label-free immunosensors were fabricated by immobilizing brucella melitensis antibody on the surface of gold nanoparticle-modified screen-printed carbon electrodes (gnp-spces). cyclic voltammetry (cv) and eis were used to characterize the brucella melitensis antigen interaction on the surface of gnp-spces with antibody. a general elec ...201323881126
construction of an expression plasmid (vector) encoding brucella melitensis outer membrane protein, a candidate for dna vaccine.dna vaccination with plasmid encoding bacterial, viral, and parasitic immunogens has been shown to be an attractive method to induce efficient immune responses. bacteria of the genus brucella are facultative intracellular pathogens for which new and efficient vaccines are needed.201326989713
diverse genetic regulon of the virulence-associated transcriptional regulator mucr in brucella abortus 2308.the ros-type regulator mucr is one of the few transcriptional regulators that have been linked to virulence in brucella. here, we show that a brucella abortus in-frame mucr deletion strain exhibits a pronounced growth defect during in vitro cultivation and, more importantly, that the mucr mutant is attenuated in cultured macrophages and in mice. the genetic basis for the attenuation of brucella mucr mutants has not been defined previously, but in the present study the genes regulated by mucr in ...201323319565
immunogenic and invasive properties of brucella melitensis 16m outer membrane protein vaccine candidates identified via a reverse vaccinology approach.brucella is the etiologic agent of brucellosis, one of the most common and widely distributed zoonotic diseases. its highly infectious nature, the insidious, systemic, chronic, debilitating aspects of the disease and the lack of an approved vaccine for human use in the united states are features that make brucella a viable threat to public health. one of the main impediments to vaccine development is identification of suitable antigens. in order to identify antigens that could potentially be use ...201323533646
osteoarticular tissue infection and development of skeletal pathology in murine brucellosis.brucellosis, a frequent bacterial zoonosis, can produce debilitating chronic disease with involvement of multiple organs in human patients. whereas acute brucellosis is well studied using the murine animal model, long-term complications of host-pathogen interaction remain largely elusive. human brucellosis frequently results in persistent, chronic osteoarticular system involvement, with complications such as arthritis, spondylitis and sacroiliitis. here, we focused on identifying infectious site ...201323519029
a foodborne outbreak of brucellosis at a police station cafeteria, lima, peru.brucella melitensis is highly infectious for humans and can be transmitted to humans in a number of epidemiological contexts. within the context of an ongoing brucellosis surveillance project, an outbreak at a peruvian police officer cafeteria was discovered, which led to active surveillance (serology, blood culture) for additional cases among 49 police officers who had also eaten there. the cohort was followed up to 18 months regardless of treatment or symptoms. active surveillance estimated th ...201323382164
immune reactivity of brucella melitensis-vaccinated rabbit serum with recombinant omp31 and dnak proteins.brucella melitensis infection is still a major health problem for human and cattle in developing countries and the middle east.201323467315
molecular epidemiology and antibiotic susceptibility of livestock brucella melitensis isolates from naryn oblast, kyrgyzstan.the incidence of human brucellosis in kyrgyzstan has been increasing in the last years and was identified as a priority disease needing most urgent control measures in the livestock population. the latest species identification of brucella isolates in kyrgyzstan was carried out in the 1960s and investigated the circulation of brucella abortus, b. melitensis, b. ovis, and b. suis. however, supporting data and documentation of that experience are lacking. therefore, typing of brucella spp. and ide ...201323469294
brucella melitensis mucr, an orthologue of sinorhizobium meliloti mucr, is involved in resistance to oxidative, detergent, and saline stresses and cell envelope modifications.brucella spp. and sinorhizobium meliloti are alphaproteobacteria that share not only an intracellular lifestyle in their respective hosts, but also a crucial requirement for cell envelope components and their timely regulation for a successful infectious cycle. here, we report the characterization of brucella melitensis mucr, which encodes a zinc finger transcriptional regulator that has previously been shown to be involved in cellular and mouse infections at early time points. mucr modulates th ...201323161025
peptide nucleic acids inhibit growth of brucella suis in pure culture and in infected murine macrophages.peptide nucleic acids (pnas) are single-stranded, synthetic nucleic acid analogues containing a pseudopeptide backbone in place of the phosphodiester sugar-phosphate. when pnas are covalently linked to cell-penetrating peptides (cpps) they readily penetrate the bacterial cell envelope, inhibit expression of targeted genes and cause growth inhibition both of gram-positive and gram-negative bacteria. however, the effectiveness of pnas against brucella, a facultative intracellular bacterial pathoge ...201323305655
induction of protective immunity against brucellosis in mice by vaccination with a combination of naloxone, alum, and heat-killed brucella melitensis 16 m.a t-helper cell type 1-specific response leads to the elimination of intracellular infection with brucella. studies have shown that naloxone (nlx) can promote a cellular immune response in this respect. the current study was carried out to evaluate the induction of protective immunity in mice against brucellosis by vaccination with a combination of nlx, alum, and heat-killed brucella melitensis 16 m (hkb).201322727892
exact alpha-error determination for two-stage sampling strategies to substantiate freedom from disease.sampling strategies to substantiate freedom from disease are important when it comes to the trade of animals and animal products. when considering imperfect tests and finite populations, sample size calculation can, however, be a challenging task. the generalized hypergeometric formula developed by cameron and baldock (1998a) offers a framework that can elegantly be extended to multi-stage sampling strategies, which are widely used to account for disease clustering at herd-level. the achieved al ...201323103193
fed batch fermentation and purification strategy for high yield production of brucella melitensis recombinant omp 28 kda protein and its application in disease diagnosis.brucellosis is a disease caused by bacteria belonging to the genus brucella. it affects cattle, goat, sheep, dog and humans. the serodiagnosis of brucellosis involves detection of antibodies generated against the lps or whole cell bacterial extracts, however these tests lack sensitivity and specificity. the present study was performed to optimize the culture condition for the production of recombinant brucella melitensis outer membrane protein 28 kda protein in e.coli via fed batch fermentation. ...201323167982
recent developments in livestock and wildlife brucellosis vaccination.live attenuated brucellosis vaccines have been available for protecting domestic livestock against brucella melitensis and b. abortus for more than 60 years. current vaccines are effective in preventing abortion and transmission of brucellosis, but poor at preventing infection or seroconversion. in addition, they can induce abortions in pregnant animals and are infectious to humans. it can be argued that current vaccines were developed empirically in that the immunological mechanism(s) of action ...201323837378
silencing of prp c (prion protein) expression does not affect brucella melitensis infection in human derived microglia cells.cellular prion proteins (prp(c)) are mainly expressed in the central nervous system where they have antioxidant effects and a role in the endocytosis of bacteria within cells. these proteins also have some crucial biological functions including roles in neurotransmission, signal transduction and programmed cell death. however, the role of prion proteins in neuronal brucella infection, specifically in the interaction of the pathogen and the host cell is controversial. in the present study, the si ...201323820446
comparison of genomes of brucella melitensis m28 and the b. melitensis m5-90 derivative vaccine strain highlights the translation elongation factor tu gene tuf2 as an attenuation-related gene.brucella melitensis causes brucellosis, a disease affecting sheep, cattle, and sometimes humans. attenuated b. melitensis strain m5-90, derived from virulent strain m28, is widely used as a live vaccine in ruminants in china. genetic differences between the strains may cast light on the mechanism of attenuation. we recently reported the complete genomic sequences of m28 and m5-90. genome organization is highly conserved between these isolates, and also with virulent strains 16 m and atcc 23457. ...201323716607
brucellosis in guangdong province, people's republic of china, 2005-2010. 201323697913
reinvestigation of the structure of brucella o-antigens.o-specific polysaccharides of brucella contain two antigenic determinants, called a and m. most of the strains express epitope a with a small amount of epitope m, whereas brucella melitensis strain 16 m expresses longer polymer consisting mostly of m-type epitopes. proposed explanation was that epitope a is defined by 1-2-linked homopolymer of n-formylperosamine (rha4nfo), while epitope m is a pentasaccharide with four 2- and one 3-substituted rha4nfo. we reinvestigated both types of structures ...201323664729
hydrophobic gentamicin-loaded nanoparticles are effective against brucella melitensis infection in mice.the clinical management of human brucellosis is still challenging and demands in vitro active antibiotics capable of targeting the pathogen-harboring intracellular compartments. a sustained release of the antibiotic at the site of infection would make it possible to reduce the number of required doses and thus the treatment-associated toxicity. in this study, a hydrophobically modified gentamicin, gentamicin-aot [aot is bis(2-ethylhexyl) sulfosuccinate sodium salt], was either microstructured or ...201323650167
brucella melitensis 16mδhfq attenuation confers protection against wild-type challenge in balb/c mice.brucellosis is a globally distributed zoonotic disease that causes animal and human diseases. although effective, the current brucella vaccines (rev.1 and m5-90) have several drawbacks. the first involves residual virulence for animals and humans and the second is the inability to differentiate natural infection from that caused by vaccination. therefore, brucella melitensis 16m hfq mutant (16mδhfq) was constructed to overcome these drawbacks. similarly to rev.1 and m5-90, 16mδhfq reduces surviv ...201323647412
the antibacterial activity of selected labiatae (lamiaceae) essential oils against brucella melitensis.brucellosis, a zoonosis caused by four species of brucella, has a high morbidity. the major cause of brucellosis worldwide is brucella melitensis. medicinal plants are considered as new antibacterial sources that could replace conventional antibiotics in the treatment of antibiotic-resistant bacteria. the aim of this study was to evaluate the efficacy of some native plants, alone and in combination with some antibiotics, in the treatment of brucellosis.201323645957
immune response and serum bactericidal activity against brucella ovis elicited using a short immunization schedule with the polymeric antigen blsomp31 in rams.brucella ovis is the etiologic agent of ovine brucellosis. the control measures for this disease are periodical diagnosis by serological tests and/or bacteriological culture and culling of positive animals. vaccination with brucella melitensis rev 1 is recommended when prevalence is high. this attenuated strain vaccine gives protection against b. ovis but it has important disadvantages associated with the development of antibodies interfering with serodiagnosis, virulence for humans and the proh ...201323643287
replication of brucella melitensis inside primary human monocytes depends on mitogen activated protein kinase signaling.the clinical course of infections caused by brucella is linked to its capacity to modulate the initial immune response of macrophages in order to ensure its intracellular replication. signal transduction pathways implicated in the survival of brucella in human cells are not completely elucidated. we herein investigated the involvement of the tlr-mapk-dependent signaling pathways in the survival of brucella in primary human monocytes using live clinical strains of brucella melitensis. b. melitens ...201323628412
evaluation of the immunogenicity and the protective efficacy in mice of a dna vaccine encoding sp41 from brucella melitensis.brucella melitensis is a facultative intracellular gram-negative bacterial pathogen that may enter the host via ingestion or inhalation, or through conjunctiva or skin abrasions. some brucella spp surface proteins (sps) play an important role in bacterial adhesion and invasion and thus represent targets for the host immune system. brucella spp surface protein with apparent molecular mass of 41 kda interacts selectively with hela cells.201323592643
congenital brucellosis in an infant.brucellosis has been reported mainly among pregnant women, and it may lead to spontaneous abortion, intrauterine fetal death, or delivery of an infected neonate. transmission through breast milk has also been described, but congenital cases are not commonly reported. we present the clinical findings, laboratory studies, treatment, and final outcome of a late prenatal transmission from a mother to her term infant of brucella melitensis biovar 1. because the maternal disease was undetected due to ...201323590322
interactions of lipopolysaccharide with lipid membranes, raft models - a solid state nmr study.lipopolysaccharide (lps) is a major component of the external leaflet of bacterial outer membranes, key pro-inflammatory factor and an important mediator of host-pathogen interactions. in host cells it activates the complement along with a pro-inflammatory response via a tlr4-mediated signalling cascade and shows preference for cholesterol-containing membranes. here, we use solid state (13)c and (31)p mas nmr to investigate the interactions of lps from three bacterial species, brucella melitensi ...201323567915
in vitro antimicrobial susceptibility of brucella melitensis isolates from sheep in an area endemic for human brucellosis in turkey.the aim of this study was to assess in vitro antimicrobial susceptibility of brucella melitensis isolates isolated from naturally infected sheep cases in an area where human brucellosis is endemic, focusing on rifampin (rif), streptomycin (sm), ciprofloxacin (cpfx), trimethoprim/sulfamethoxazole (tmp/smz), gentamicin (gm) and tetracycline (tc) and on 11 other antimicrobials. the identification and typing of brucella isolates were carried out using standard classification tests and polymerase cha ...201323545462
erythritol triggers expression of virulence traits in brucella melitensis.erythritol is a four-carbon sugar preferentially utilized by brucella spp. the presence of erythritol in the placentas of goats, cows, and pigs has been used to explain the localization of brucella to these sites and the subsequent accumulation of large amounts of bacteria, eventually leading to abortion. here we show that brucella melitensis will also localize to an artificial site of erythritol within a mouse, providing a potential model system to study the pathogenesis of brucella abortion. i ...201323421980
sustained and differential antibody responses to virulence proteins of brucella melitensis during acute and chronic infections in human brucellosis.brucellosis is an important zoonotic disease caused primarily by the bacterial pathogens brucella melitensis and b. abortus. the pathogens cause debilitating febrile illness that can progress into a long-lasting disease with severe complications in humans. understanding the mechanisms by which the host immune system responds to the infection will provide important information on the pathogenesis and development of differential diagnostic assays. in this study, a protein microarray was used to ev ...201323224716
the effects of mucr on expression of type iv secretion system, quorum sensing system and stress responses in brucella melitensis.mucr is a transcriptional regulator in many bacterial pathogens and is required for virulence in mice and macrophages, resistance to stress responses, and modification of the cell envelope in brucella spp. to determine why the mucr deleted mutant is attenuated in vivo and in vitro, we performed rna-seq analysis using brucella melitensis rna obtained from b. melitensis 16m and 16mδmucr grown under the same conditions. we found 442 differentially expressed genes; 310 were over expressed, and 132 w ...201323932078
aerosol-induced brucellosis increases tlr-2 expression and increased complexity in the microanatomy of astroglia in rhesus macaques.brucella melitensis, a bacterial pathogen and agent of epizootic abortion causes multiple pathologies in humans as well as a number of agriculturally important animal species. clinical human brucellosis manifests as a non-specific, chronic debilitating disease characterized by undulant fever, arthropathies, cardiomyopathies and neurological sequelae. these symptoms can occur acutely for a few weeks or persist for months to years. within the brain, endothelial and glial cells can be infected lead ...201324350061
brucella induces an unfolded protein response via tcpb that supports intracellular replication in macrophages.brucella melitensis is a facultative intracellular bacterium that causes brucellosis, the most prevalent zoonosis worldwide. the brucella intracellular replicative niche in macrophages and dendritic cells thwarts immune surveillance and complicates both therapy and vaccine development. currently, host-pathogen interactions supporting brucella replication are poorly understood. brucella fuses with the endoplasmic reticulum (er) to replicate, resulting in dramatic restructuring of the er. this er ...201324339776
skeletal involvement of brucella melitensis in children: a systematic review.brucellosis is a protean disease and should be excluded in any febrile child with a constellation of symptoms such as fever, malaise, sweating, arthralgia, and joint swelling in endemic areas. skeletal system involvement is the most common source of complaints in brucellosis. the frequency of skeletal involvement in children is 6.4% to 73.5%. there are some controversies regarding the most common sites of involvement: sacroiliac versus peripheral joints. in the vast majority of cases, peripheral ...201324293781
prematurity due to maternal brucella infection and review of the literature.brucellosis is a zoonosis caused by ingestion of unpasteurized milk or other dairy products from infected animals or through close contact with their secretions. human-to-human transmission, which is rare, has been reported in association with blood transfusion, bone marrow transplantation, transplacental or perinatal exposure, and breastfeeding. in the neonatal period, congenital brucellosis, which is an extremely rare condition, can lead to serious clinical consequences with a high morbidity a ...201324292039
cd8 knockout mice are protected from challenge by vaccination with wr201, a live attenuated mutant of brucella melitensis.cd8+ t cells have been reported to play an important role in defense against b. abortus infection in mouse models. in the present report, we use cd8 knockout mice to further elucidate the role of these cells in protection from b. melitensis infection. mice were immunized orally by administration of b. melitensis wr201, a purine auxotrophic attenuated vaccine strain, then challenged intranasally with b. melitensis 16m. in some experiments, persistence of wr201 in the spleens of cd8 knockout mice ...201324288554
an unusual case of neurobrucellosis presenting as demyelination disorder.brucellosis is a public health problem in most countries in the mediterranean. involvement of the central nervous system is seen in 4-13% of patients with brucellosis. a 13-year-old girl was admitted because of gait disturbance, diplopia, and dizziness. her complaints began about 1.5 years ago. the second symptomatic episode repeated about three months ago and the third two months ago. in total, attacks repeated 3 times over 1.5 years. the magnetic resonance imaging (mri) and the clinical featur ...201324192684
deletion of the gi-2 integrase and the wbka flanking transposase improves the stability of brucella melitensis rev 1 vaccine.brucella melitensis rev 1 is the best vaccine available for the prophylaxis of small ruminant brucellosis and, indirectly, for reducing human brucellosis. however, rev 1 shows anomalously high rates of spontaneous dissociation from smooth (s) to rough (r) bacteria, the latter being inefficacious as vaccines. this s-r instability results from the loss of the o-polysaccharide. to overcome this problem, we investigated whether some recently described mechanisms promoting mutations in o-polysacchari ...201324176078
effect of medium ph on antibiotic activity against syrian brucella spp. isolates.brucellosis is an endemic zoonosis in syria, affecting large numbers of animals. there are an increasing number of cases in humans. brucella is a facultative intracellular pathogen, a small, non-motile, gram-negative coccobacillus, which causes abortion in domestic animals and a febrile illness in humans.201324174696
hepatic brucelloma.we present a case of hepatic abscess caused by brucella melitensis (or hepatic brucelloma) diagnosed in a 59-year-old man 33 years after an episode of acute brucellosis that had completely resolved. recovery from symptoms and a decrease in lesion size seen on radiological assessment were achieved through prolonged combined antibiotic therapy, without the need for surgery. hepatic brucelloma is a rare complication of brucellosis, which is the most common zoonosis globally, mainly occurring in spe ...201324156899
draft genome sequence of brucella melitensis strain admas-g1, isolated from placental fluids of an aborted goat.here, we report the draft genome sequence and annotation of the brucella melitensis strain designated admas-g1, isolated from placental fluids of an aborted goat. the length of the genome is 3,284,982 bp, with a 57.3% gc content. a total of 3,325 protein-coding genes and 63 rna genes were predicted.201324115541
in vitro drug resistance of clinical isolated brucella against antimicrobial agents.to explore the antibiotic resistance of brucella melitensis and instruct rational use of antimicrobial agents in clinical treatment of brucella infection.201324083592
laboratory exposure to brucella melitensis in denmark: a prospective study.brucella species are a frequent cause of laboratory-acquired infections. this report describes the handling of a laboratory exposure of 17 laboratory staff members exposed to brucella melitensis in a large microbiology laboratory in a brucella-non-endemic area. we followed the us centers for disease control and prevention guidelines, but, of 14 staff members classified as high-risk exposure, none accepted post-exposure prophylaxis. however, in a period of 6 months of follow-up, none of the expos ...201324070633
ex vivo innate immune cytokine signature of enhanced risk of relapsing brucellosis.brucellosis, a zoonotic infection caused by one of the gram-negative intracellular bacteria of the brucella genus, is an ongoing public health problem in perú. while most patients who receive standard antibiotic treatment recover, 5-40% suffer a brucellosis relapse. in this study, we examined the ex vivo immune cytokine profiles of recovered patients with a history of acute and relapsing brucellosis.201324040434
brucellosis in a renal transplant recipient.brucellosis is one of the most common systemic zoonotic diseases transmitted by consumption of unpasteurized dairy products or by occupational contact with infected animals. brucellosis is rare in renal transplant recipients. only 3 cases have been reported in the literature. we report a case of brucellosis with hematologic and hepatobiliary complications in a patient 3 years after renal transplantation. the mean time from transplantation to the diagnosis of brucellosis in these 4 reported patie ...201324034171
modelling risk aversion to support decision-making for controlling zoonotic livestock diseases.zoonotic infectious livestock diseases are becoming a significant burden for both animal and human health and are rapidly gaining the attention of decision-makers who manage public health programmes. if control decisions have only monetary components, governments are generally regarded as being risk-neutral and the intervention strategy with the highest expected benefit (lowest expected net costs) should be preferred. however, preferences will differ and alternative intervention plans will preva ...201324761718
brucella endocarditis of pseudoaneurysm of an aortic composite graft.the occurrence of brucella endocarditis following bentall operation is a rare and life threatening condition, particularly when it is complicated by development of a pseudoaneurysm. here we present a 40-year-old veterinarian with bicuspid aortic valve, who developed type a aortic root dissection and required bentall operation. his past medical history was positive for an episode of treated brucellosis. four months after the operation, he developed signs, symptoms and serological findings of bruc ...201324459566
epidemiology of brucellosis in domestic animals caused by brucella melitensis, brucella suis and brucella abortus.brucellosis is a disease that causes severe economic losses for livestock farms worldwide. brucella melitensis, b. abortus and b. suis, which are transmitted between animals both vertically and horizontally, cause abortion and infertility in their primary natural hosts - goats and sheep (b. melitensis), cows (b. abortus) and sows (b. suis). brucella spp. infect not only their preferred hosts but also other domestic and wild animal species, which in turn can act as reservoirs of the disease for o ...201323837364
protective effect of a dna vaccine containing an open reading frame with homology to an abc-type transporter present in the genomic island 3 of brucella abortus in balb/c mice.the immunogenicity of a dna vaccine containing an open reading frame (orf) of genomic island 3 (gi-3), specific for brucella abortus and brucella melitensis, has been examined. intramuscular injection of plasmid dna carrying the open reading frame with homology to an abc-type transporter (pv278a) into balb/c mice elicited both humoral and cellular immune responses. mice injected with pv278a had a dominant immunoglobulin g2a (igg2a) response. this dna vaccine elicited a t-cell-proliferative respo ...201323834811
investigating genetic diversity of brucella abortus and brucella melitensis in italy with mlva-16.despite the eradication of brucellosis from most of europe, the disease remains relatively common in a variety of livestock in southern european countries. it is therefore surprising that with such high prevalence rates, there have been few genetic characterizations of brucellosis outbreaks in this region. we conducted a genetic assessment of 206 isolates of brucella abortus and b. melitensis from italy using variable number tandem repeats (vntrs). we determined genetic diversity and geographic ...201323831636
a duplex pcr for rapid and simultaneous detection of brucella spp. in human blood samples.to design a duplex pcr for rapid and simultaneous detection of brucella species. in human blood samples.201323711705
importance of identification and typing of brucellae from west african cattle: a review.bovine brucellosis is an endemic infectious disease which can impact cattle productivity and welfare negatively, as well as human health. sufficient knowledge on its epidemiology, particularly on species and biotypes of brucella at national and/or regional scale are important to set up and implement efficient control measures against brucellosis in a "one health" perspective. the main objective of this review was to investigate available literature on strains of brucella in order to provide a st ...201323499188
serologic detection of antibodies to brucella spp. using a commercial elisa in cattle in grenada, west indies.bovine brucellosis, caused mainly by brucella abortus, a zoonotic bacterium, has been reported from many areas of the world, including central and south america, and the caribbean island state of trinidad and tobago. although brucellosis has been eradicated from domestic cattle in canada it still exists in one or two herds in the united states. serological tests are important in estimating prevalence of brucella exposure in order to target eradication programmes. in this study, serum samples fro ...201323959493
reverse line blot macroarray for simultaneous detection and characterization of four biological warfare agents.the need for a rapid detection and characterization of biowarfare (bw) agents cannot be over emphasized. with diverse array of potential bw pathogen available presently, rapid identification of the pathogen is crucial, so that specific therapy and control measures can be initiated. we have developed a multiplex polymerase chain reaction based reverse line blot macroarray to simultaneously detect four pathogens of bw importance viz. bacillus anthracis, yersinia pestis, brucella melitensis and bur ...201324426077
mechanism of bacterial interference with tlr4 signaling by brucella toll/interleukin-1 receptor domain-containing protein tcpb.upon activation of toll-like receptors (tlrs), cytoplasmic toll/interleukin-1 receptor (tir) domains of the receptors undergo homo- or heterodimerization. this in turn leads to the recruitment of adaptor proteins, activation of transcription factors, and the secretion of pro-inflammatory cytokines. recent studies have described the tir domain-containing protein from brucella melitensis, tcpb (btpa/btp1), to be involved in virulence and suppression of host innate immune responses. tcpb interferes ...201324265315
cloning, expression, purification, crystallization and preliminary x-ray crystallographic analysis of the tir domain from the brucella melitensis tir-domain-containing protein tcpb.in mammals, toll-like receptors (tlrs) recognize conserved microbial molecular signatures and induce an early innate immune response in the host. tlr signalling is mediated by interactions between the cytosolic tir (toll/interleukin-1 receptor) domains of the receptor and the adaptor proteins. increasingly, it is apparent that pathogens target this interaction via pathogen-expressed tir-domain-containing proteins to modulate immune responses. a tir-domain-containing protein tcpb has been reporte ...201324100574
quorum sensing and self-quorum quenching in the intracellular pathogen brucellamelitensis.brucella quorum sensing has been described as an important regulatory system controlling crucial virulence determinants such as the virb type iv secretion system and the flagellar genes. however, the basis of quorum sensing, namely the production of autoinducers in brucella has been questioned. here, we report data obtained from the use of a genetic tool allowing the in situ detection of long-chain n-acyl-homoserine lactones (ahl) activity at single bacterium level in brucella melitensis. these ...201324349302
detection of virulence genes (bvfa, virb and ure) in brucella melitensis isolated from aborted fetuses of sheep and goats.brucella, causative of brucellosis, has some potential virulence factors involved in brucella replication and its strategies to circumvent the immune response. one of them is the virb gene that encodes the type iv secretion system proteins (t4ss) involved in intracellular replication of organism. brucella virulence factor a (bvfa), and urease (ure) has also been described as being implicated in survival, and virulence in the hosts. the aim of this study was to investigate the b. melitensis virul ...201325848512
in vivo differences in the virulence, pathogenicity, and induced protective immunity of wboa mutants from genetically different parent brucella spp.to explore the effects of the genetic background on the characteristics of wboa gene deletion rough mutants generated from different parent brucella sp. strains, we constructed the rough-mutant strains brucella melitensis 16 m-mb6, b. abortus 2308-sb6, b. abortus s19-rb6, and b. melitensis ni-nb6 and evaluated their survival, pathogenicity, and induced protective immunity in mice and sheep. in mice, the survival times of the four mutants were very different in the virulence assay, from less than ...201323239800
innate immune recognition of flagellin limits systemic persistence of brucella.brucella are facultative intracellular bacteria that cause chronic infections by limiting innate immune recognition. it is currently unknown whether brucella flic flagellin, the monomeric subunit of flagellar filament, is sensed by the host during infection. here, we used two mutants of brucella melitensis, either lacking or overexpressing flagellin, to show that flic hinders bacterial replication in vivo. the use of cells and mice genetically deficient for different components of inflammasomes ...201323227931
brucella bior regulator defines a complex regulatory mechanism for bacterial biotin metabolism.the enzyme cofactor biotin (vitamin h or b7) is an energetically expensive molecule whose de novo biosynthesis requires 20 atp equivalents. it seems quite likely that diverse mechanisms have evolved to tightly regulate its biosynthesis. unlike the model regulator bira, a bifunctional biotin protein ligase with the capability of repressing the biotin biosynthetic pathway, bior has been recently reported by us as an alternative machinery and a new type of gntr family transcriptional factor that ca ...201323729648
cross-institute evaluations of inhibitor-resistant pcr reagents for direct testing of aerosol and blood samples containing biological warfare agent dna.rapid pathogen detection is crucial for the timely introduction of therapeutics. two groups (one in the united kingdom and one in the united states) independently evaluated inhibitor-resistant pcr reagents for the direct testing of substrates. in the united kingdom, a multiplexed bacillus anthracis (target) and bacillus subtilis (internal-control) pcr was used to evaluate 4 reagents against 5 pcr inhibitors and down-selected the taqman fast virus 1-step master mix (life technologies inc.). in th ...201424334660
evaluation in mice of brucella ovis attenuated mutants for use as live vaccines against b. ovis infection.brucella ovis causes ram contagious epididymitis, a disease for which a specific vaccine is lacking. attenuated brucella melitensis rev 1, used as vaccine against ovine and caprine brucellosis caused by b. melitensis, is also considered the best vaccine available for the prophylaxis of b. ovis infection, but its use for this purpose has serious drawbacks. in this work, two previously characterized b. ovis attenuated mutants (δomp25d and δomp22) were evaluated in mice, in comparison with b. melit ...201424898325
the inva gene of brucella melitensis is involved in intracellular invasion and is required to establish infection in a mouse model.some of the mechanisms underlying the invasion and intracellular survival of b. melitensis are still unknown, including the role of a subfamily of nudix enzymes, which have been described in other bacterial species as invasins and are present in brucella spp. we have generated a mutation in the coding gene of one of these proteins, the inva gene (bmei0215) of b. melitensis strain 133, to understand its role in virulence. hela cell invasion results showed that mutant strain survival was decreased ...201424667775
fad binding, cobinamide binding and active site communication in the corrin reductase (cobr).adenosylcobalamin, the coenzyme form of vitamin b12, is one nature's most complex coenzyme whose de novo biogenesis proceeds along either an anaerobic or aerobic metabolic pathway. the aerobic synthesis involves reduction of the centrally chelated cobalt metal ion of the corrin ring from co(ii) to co(i) before adenosylation can take place. a corrin reductase (cobr) enzyme has been identified as the likely agent to catalyse this reduction of the metal ion. herein, we reveal how brucella melitensi ...201424909839
bartonella henselae endocarditis in laos - 'the unsought will go undetected'.both endocarditis and bartonella infections are neglected public health problems, especially in rural asia. bartonella endocarditis has been described from wealthier countries in asia, japan, korea, thailand and india but there are no reports from poorer countries, such as the lao pdr (laos), probably because people have neglected to look.201425503777
abortion in cattle due to infection with staphylococcus lugdunensis.an aborted fetus of 7 months gestation, the associated placenta, and a single blood sample from the dam were submitted for diagnostic investigation to the diagnostic laboratory of the lombardy and emilia-romagna experimental zooprophylactic institute in parma, italy. the serum was negative for neospora caninum, coxiella burnetii, chlamydophila abortus, bovine herpesvirus 1 (bhv-1), bovine viral diarrhea virus (bvdv), brucella abortus, and brucella melitensis. fetal tissues and placental cotyledo ...201425292193
inactivation of bacterial and viral biothreat agents on metallic copper surfaces.in recent years several studies in laboratory settings and in hospital environments have demonstrated that surfaces of massive metallic copper have intrinsic antibacterial and antiviral properties. microbes are rapidly inactivated by a quick, sharp shock known as contact killing. the underlying mechanism is not yet fully understood; however, in this process the cytoplasmic membrane is severely damaged. pathogenic bacterial and viral high-consequence species able to evade the host immune system a ...201425100640
seroprevalence of brucellosis in sheep and isolation of brucella abortus biovar 6 in kassala state, eastern sudan.brucellosis is one of the important zoonotic diseases among livestock. this study was carried out to estimate the prevalence of brucellosis and isolate brucella spp. in sheep in kassala state in the east of sudan. two thousand and five serum samples were randomly collected from nine different localities. all serum samples were examined by the rose bengal plate test (rbpt) and the modified rbpt (mrbpt). forty-three (2.15%, 95% confidence interval [ci]: 1.6,3.0) and 68 (3.4%, 95% ci: 2.6, 4.2) sam ...201425812219
advancement of knowledge of brucella over the past 50 years.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 u ...201424981716
a repa-based elisa for discriminating cattle vaccinated with brucella suis 2 from those naturally infected with brucella abortus and brucella melitensis.the commonest ways of diagnosing brucellosis in animals include the rose-bengal plate agglutination test, the buffered plate agglutination test (bpa), the slide agglutination test, the complement fixation test, and the indirect enzyme linked immunosorbent assay (i-elisa). however, these methods cannot discriminate the brucella vaccine strain (brucella suis strain 2; b. suis s2) from naturally acquired virulent strains. of the six common brucella species, brucella melitensis, brucella abortus, an ...201424941369
serological survey of brucella canis in dogs in urban harare and selected rural communities in zimbabwe.a cross-sectional study was conducted in order to detect antibodies for brucella canis (b. canis) in dogs from urban harare and five selected rural communities in zimbabwe. sera from randomly selected dogs were tested for antibodies to b. canis using an enzyme-linked immunosorbent assay. overall, 17.6% of sera samples tested (57/324, 95% ci: 13.5-21.7) were positive for b. canis antibodies. for rural dogs, seroprevalence varied from 11.7% - 37.9%. rural dogs recorded a higher seroprevalence (20. ...201424830899
serological survey of <i>brucella canis</i> in dogs in urban harare and selected rural communities in zimbabwe.a cross-sectional study was conducted in order to detect antibodies for brucella canis (b. canis) in dogs from urban harare and five selected rural communities in zimbabwe. sera from randomly selected dogs were tested for antibodies to b. canis using an enzyme-linked immunosorbent assay. overall, 17.6% of sera samples tested (57/324, 95% ci: 13.5-21.7) were positive for b. canis antibodies. for rural dogs, seroprevalence varied from 11.7% - 37.9%. rural dogs recorded a higher seroprevalence (20. ...201428235300
seroprevalence for coxiella burnetii, francisella tularensis, brucella abortus and brucella melitensis in austrian adults: a cross-sectional survey among military personnel and civilians.the prevalence of coxiella burnetii, francisella tularensis, brucella abortus, and brucella melitensis infections in austria and the exposure risk of military personnel were assessed in an exploratory nationwide cross-sectional seroprevalence survey in 526 healthy adult individuals, 222 of which were soldiers and 304 were civilians. screening for iga/igg antibodies to c. burnetii (phase i) and igg/igm antibodies to c. burnetii (phase ii), and to f. tularensis was done with commercial enzyme-link ...201424572607
comparative whole genome analysis of six diagnostic brucellaphages.whole genome sequencing of six diagnostic brucellaphages, tbilisi (tb), firenze (fz), weybridge (wb), s708, berkeley (bk) and r/c, was followed with genomic comparisons including recently described genomes of the tb phage from mexico (tbm) and pr phage to elucidate genomic diversity and candidate host range determinants. comparative whole genome analysis revealed high sequence homogeneity among these brucellaphage genomes and resolved three genetic groups consistent with defined host range pheno ...201424530704
isolation and identification of bovine brucella isolates from pakistan by biochemical tests and pcr.brucellosis is endemic in bovines in pakistan. the brucella species and biovars involved, however, are unknown. the objectives of the present study were to isolate and characterize brucellae from seropositive milk samples, aborted fetuses, and vaginal swabs of cattle and buffaloes which had recently aborted. the seropositive milk samples, aborted fetuses, and vaginal swabs of cattle and buffaloes were collected from the potohar plateau, pakistan. isolation of brucellae was done on modified farre ...201423868548
genetic polymorphism characteristics of brucella canis isolated in china.in china, brucellosis is an endemic disease typically caused by brucella melitensis infection (biovars 1 and 3). brucella canis infection in dogs has not traditionally recognized as a major problem. in recent years however, brucellosis resulting from brucella canis infection has also been reported, suggesting that infections from this species may be increasing. data concerning the epidemiology of brucellosis resulting from brucella canis infection is limited. therefore, the purpose of this study ...201424465442
evaluation of different enzyme-linked immunosorbent assays for the diagnosis of brucellosis due to brucella melitensis in sheep.six serological assays for the diagnosis of ovine brucellosis, due to brucella melitensis were evaluated. reference serum samples from sheep of known b. melitensis infection status (n=118) were assessed using the rose bengal test (rbt), complement fixation test (cft) and four commercial enzyme-linked immunosorbent assays (elisas), including two indirect elisas (ielisas), one competitive elisa (celisa) and one blocking elisa (belisa). the highest differential positive rates (dpr) were obtained wi ...201424456797
brucella melitensis shunt infection. 201424441347
antimicrobial susceptibility data for brucella melitensis isolates cultured from uk patients. 201424440739
splenic abscess due to brucellosis: a case report and a review of the literature.splenic abscess due to acute brucellosis is a rare event. we report a case of multiple splenic abscesses caused by brucella melitensis in a 45-year-old woman and review the english language literature based on a pubmed/medline search of the last 50 years. the majority of the cases published in the literature were due to b. melitensis and a splenectomy was required in half of the cases. antibiotics alone without surgical intervention can be successful in the treatment of patients with splenic bru ...201424433982
immunotherapeutics to prevent the replication of brucella in a treatment failure mouse model.outer membrane vesicles (omvs) from brucella melitensis and irradiated brucella neotomae have been shown to be effective vaccines against a b. melitensis challenge in a mouse model. the present study evaluates the efficacy of these two vaccines as immuno-therapeutics in combination with conventional antibiotics against a b. melitensis infection. balb/c mice chronically infected with b. melitensis were treated for 4 weeks with doxycycline and gentamicin and vaccinated twice during the course of t ...201424397905
increasing threat of brucellosis to low-risk persons in urban settings, china.cases of brucellosis were diagnosed in 3-month-old twins and their mother. an epidemiologic survey suggested that raw sheep or goat meat might be the source of brucella melitensis infection. this finding implies that the increasing threat of brucellosis might affect low-risk persons in urban settings in china.201424377827
innocuity and immune response to brucella melitensis rev.1 vaccine in camels (camelus dromedarius).a field trial was conducted in a camel brucellosis-free herd to evaluate antibody response to the brucella melitensis rev.1 vaccine in camels and assess shedding of the vaccine strain in milk. twenty eight camels were divided into four groups according to their age and vaccination route. groups a (n=3) and b (n=3) consisted of non-pregnant lactating female camels, vaccinated through subcutaneous and conjunctival routes, respectively. groups c (n=10) consisted of 8-11 months old calves vaccinated ...201426623347
evaluation of humoral and cellular immune responses to bp26 and omp31 epitopes in the attenuated brucella melitensis vaccinated sheep.in recent years, the number of cases of human brucellosis has been increasing by approximately 10% per year in china. most cases were caused by brucella melitensis through contacts with infected sheep, goats or their products. an attenuated b. melitensis vaccine m5-90 is currently used to vaccinate both animals in china. this vaccine has not been investigated for critical parameters such as immune response and its association with protective efficacy. in this study, humoral and cellular immune r ...201424370708
three-dimensional (3d) structure prediction of the american and african oil-palms β-ketoacyl-[acp] synthase-ii protein by comparative modelling.the fatty-acid profile of the vegetable oils determines its properties and nutritional value. palm-oil obtained from the african oil-palm [elaeis guineensis jacq. (tenera)] contains 44% palmitic acid (c16:0), but, palm-oil obtained from the american oilpalm [elaeis oleifera] contains only 25% c16:0. in part, the b-ketoacyl-[acp] synthase ii (kasii) [ec: 2.3.1.179] protein is responsible for the high level of c16:0 in palm-oil derived from the african oil-palm. to understand more about e. guineen ...201424748752
cold shock protein a plays an important role in the stress adaptation and virulence of brucella melitensis.brucella melitensis is a facultative intracellular pathogen that mainly resides within macrophages. the mechanisms employed by brucella to adapt to harsh intracellular environments and survive within host macrophages are not clearly understood. here, we constructed a cspa gene deletion mutant, niδcspa, that did not exhibit any discernible growth defect at a normal culture temperature (37 °c) or at a low temperature (15 °c). however, expression of the cspa gene in brucella was induced by cold, ac ...201424661136
crystal structure and biochemical studies of brucella melitensis 5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase.the prokaryotic 5'-methylthioadenosine/s-adenosylhomocysteine nucleosidase (mtan) catalyzes the irreversible cleavage of the glycosidic bond in 5'-methylthioadenosine (mta) and s-adenosylhomocysteine (sah), a process that plays a key role in several metabolic pathways. its absence in all mammalian species has implicated this enzyme as a promising target for antimicrobial drug design. here, we report the crystal structure of bmmtan in complex with its product adenine at a resolution of 2.6 å dete ...201424657441
humoral immunity and cd4+ th1 cells are both necessary for a fully protective immune response upon secondary infection with brucella melitensis.brucella spp are intracellular bacteria that cause brucellosis, one of the most common zoonoses in the world. given the serious medical consequences of this disease, a safe and effective human vaccine is urgently needed. efforts to develop this vaccine have been hampered by our lack of understanding of what constitutes a protective memory response against brucella. in this study, we characterize the cells and signaling pathways implicated in the generation of a protective immune memory response ...201424646742
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