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spectroscopic and kinetic investigation of the reactions of peroxyacetic acid with burkholderia pseudomallei catalase-peroxidase, katg.catalase-peroxidases or katgs can utilize organic peroxyacids and peroxides instead of hydrogen peroxide to generate the high-valent ferryl-oxo intermediates involved in the catalase and peroxidase reactions. in the absence of peroxidatic one-electron donors, the ferryl intermediates generated with a low excess (10-fold) of peroxyacetic acid (paa) slowly decay to the ferric resting state after several minutes, a reaction that is demonstrated in this work by both stopped-flow uv-vis absorption me ...201324044787
improved diagnosis of melioidosis using a 2-dimensional immunoarray.melioidosis is caused by the gram negative bacterium burkholderia pseudomallei. the gold standard for diagnosis is culture, which requires at least 3-4 days obtaining a result, hindering successful treatment of acute disease. the existing indirect haemagglutination assay (iha) has several disadvantages, in that approximately half of patients later confirmed culture positive are not diagnosed at presentation and a subset of patients are persistently seronegative. we have developed 2 serological a ...201324041552
a case report of melioidosis in a diabetic patient in a union territory.melioidosis is an emerging disease in india. cases have also been reported from south east asia, australia and japan. major risk factors for melioidosis are diabetes mellitus, preexisting renal disease and thalassemia. exposure to contaminated soil and water are also significant occupational hazards associated with the disease. a patient with diabetes of six years duration on regular medication presented with fever, generalised myalgia and headache for a week. blood and bone marrow culture yield ...201324039633
in vitro activities of amoxicillin-clavulanate, doxycycline, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole against biofilm of brazilian strains of burkholderia pseudomallei.this study aimed at investigating the in vitro activities of amoxicillin-clavulanate, doxycycline, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole against burkholderia pseudomallei in planktonic and biofilm forms, through broth microdilution and resazurin-based viability staining, respectively. in planktonic growth, the strains were susceptible to the drugs, while in biofilm growth, significantly higher antimicrobial concentrations were required, especially for ceftazidime and imipenem, ...201324002089
exploiting the burkholderia pseudomallei acute phase antigen bpsl2765 for structure-based epitope discovery/design in structural vaccinology.we solved the crystal structure of burkholderia pseudomallei acute phase antigen bpsl2765 in the context of a structural vaccinology study, in the area of melioidosis vaccine development. based on the structure, we applied a recently developed method for epitope design that combines computational epitope predictions with in vitro mapping experiments and successfully identified a consensus sequence within the antigen that, when engineered as a synthetic peptide, was selectively immunorecognized t ...201323993463
in vitro antimicrobial susceptibility of clinical and environmental strains of burkholderia pseudomallei from brazil. 201323993065
endogenous α2-antiplasmin is protective during severe gram-negative sepsis (melioidosis).α2-antiplasmin (a2ap) is a major inhibitor of fibrinolysis by virtue of its capacity to inhibit plasmin. although the fibrinolytic system is strongly affected by infection, the functional role of a2ap in the host response to sepsis is unknown.201323992406
x-box binding protein 1 (xbp1s) is a critical determinant of pseudomonas aeruginosa homoserine lactone-mediated apoptosis.pseudomonas aeruginosa infections are associated with high mortality rates and occur in diverse conditions including pneumonias, cystic fibrosis and neutropenia. quorum sensing, mediated by small molecules including n-(3-oxo-dodecanoyl) homoserine lactone (c12), regulates p. aeruginosa growth and virulence. in addition, host cell recognition of c12 initiates multiple signalling responses including cell death. to gain insight into mechanisms of c12-mediated cytotoxicity, we studied the role of en ...201323990788
comparative assessment of the intracellular survival of the burkholderia pseudomallei bopc mutant.burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative saprophytic bacterium capable of surviving within phagocytic cells. to assess the role of bopc (a type iii secreted effector protein) in the pathogenesis of b. pseudomallei, a b. pseudomallei bopc mutant was used to infect j774a.1 macrophage-like cells. the bopc mutant showed significantly reduced intracellular survival in infected macrophages compared to wild-type b. pseudomallei. in addition, the bopc mutant disp ...201323990305
burkholderia pseudomallei suppresses caenorhabditis elegans immunity by specific degradation of a gata transcription factor.burkholderia pseudomallei is a gram-negative soil bacterium that infects both humans and animals. although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. to gain insights into the host defense responses to b. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected caenorhabditis elegans and identified ∼6% ...201323980181
in vitro activity of tebipenem against burkholderia pseudomallei. 201323978354
the condition-dependent transcriptional landscape of burkholderia pseudomallei.burkholderia pseudomallei (bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 mb with two large circular chromosomes (1 and 2). to comprehensively delineate the bp transcriptome, we integrated whole-genome tiling array expression data of bp exposed to >80 diverse physical, chemical, and biological conditions. our results provide direct experimental support for the strand-specific expression of 5,4 ...201324068961
neurologic melioidosis.melioidosis is an important cause of morbidity and mortality in northern australia and southeast asia. diagnosis is best made by isolation of burkholderia pseudomallei from clinical specimens. a variety of clinical presentations are described, including neurologic disease. the aim of this study was to review admissions with confirmed neurologic melioidosis to a regional hospital in a region to which melioidosis is endemic during 1995-2011. there were 12 culture-confirmed cases of neurologic meli ...201323836574
a rare cause of septic arthritis: melioidosis.melioidosis is a pyogenic infection with high mortality caused by the bacterium burkholderia pseudomallei. as the clinical presentation is not distinctive, a high index of clinical suspicion is required for diagnosis. we present a case of a 50-year-old farmer who was diabetic and a chronic alcoholic, who presented to us with pneumonia, followed by septic arthritis. he was ultimately diagnosed as having melioidosis.201324067292
less is more: burkholderia pseudomallei and chronic melioidosis.the gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. once considered an esoteric tropical disease confined to southeast asia and northern australia, research on b. pseudomallei has recently gained global prominence due to its classification as a potential bioterrorism agent by countries such as the united states and also by increasing numbers of case reports from regions where it is not endemic. an enviro ...201324065633
an improved selective culture medium enhances the isolation of burkholderia pseudomallei from contaminated specimens.burkholderia pseudomallei is a gram-negative environmental bacterium found in tropical climates that causes melioidosis. culture remains the diagnostic gold standard, but isolation of b. pseudomallei from heavily contaminated sites, such as fecal specimens, can be difficult. we recently reported that b. pseudomallei is capable of infecting the gastrointestinal tract of mice and suggested that the same may be true in humans. thus, there is a strong need for new culture techniques to allow for eff ...201324062483
survey of innate immune responses to burkholderia pseudomallei in human blood identifies a central role for lipopolysaccharide.b. pseudomallei is a gram-negative bacterium that causes the tropical infection melioidosis. in northeast thailand, mortality from melioidosis approaches 40%. as exemplified by the lipopolysaccharide-toll-like receptor 4 interaction, innate immune responses to invading bacteria are precipitated by activation of host pathogen recognition receptors by pathogen associated molecular patterns. human melioidosis is characterized by up-regulation of pathogen recognition receptors and pro-inflammatory c ...201324303060
cytidine derivatives as ispf inhibitors of burkolderia pseudomallei.published biological data suggest that the methyl erythritol phosphate (mep) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. one highly conserved enzyme in the mep pathway is 2c-methyl-d-erythritol 2,4-cyclodiphosphate synthase (ispf). fragment-bound complexes of ispf from burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fragm ...201324157367
glyburide reduces bacterial dissemination in a mouse model of melioidosis.burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired gram-negative sepsis in northeast thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. we showed in a previous cohort study that patients taking glyburide ( = glibenclamide) prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. we sought to define the mechanism underlying this observation in a m ...201324147174
case of paraspinal collection due to burkholderia pseudomallei. 201324132451
identification of a predicted trimeric autotransporter adhesin required for biofilm formation of burkholderia pseudomallei.the autotransporters are a large and diverse family of bacterial secreted and outer membrane proteins, which are present in many gram-negative bacterial pathogens and play a role in numerous environmental and virulence-associated interactions. as part of a larger systematic study on the autotransporters of burkholderia pseudomallei, the causative agent of the severe tropical disease melioidosis, we have constructed an insertion mutant in the bpss1439 gene encoding an unstudied predicted trimeric ...201324223950
evaluation of aromatic plants and compounds used to fight multidrug resistant infections.traditional medicine plays a vital role for primary health care in india, where it is widely practiced to treat various ailments. among those obtained from the healers, 78 medicinal plants were scientifically evaluated for antibacterial activity. methanol extract of plants (100  μ g of residue) was tested against the multidrug resistant (mdr) gram-negative and gram-positive bacteria. forty-seven plants showed strong activity against burkholderia pseudomallei (strain tes and khw) and staphylococc ...201324223059
cervical abscesses due to co-infection with burkholderia pseudomallei, salmonella enterica serovar stanley and mycobacterium tuberculosis in a patient with diabetes mellitus.infections due to mycobacterium tuberculosis, burkholderia pseudomallei and non-typhoidal salmonella cause significant morbidity and mortality throughout the world. these intracellular pathogens share some common predisposing factors and clinical features. co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.201324209898
sequence determination of burkholderia pseudomallei strain nctc 13392 colony morphology variants.burkholderia pseudomallei is a biothreat and the causative agent of melioidosis. there are at least seven known colony morphotypes of b. pseudomallei that appear to have different virulence properties in animal models. we report the genome sequence of b. pseudomallei strain nctc 13392 and the genomic variations of its eight morphotype derivatives.201324201202
the in vitro antibiotic susceptibility of malaysian isolates of burkholderia pseudomallei.acute melioidosis may present as localised or septicaemic infections and can be fatal if left untreated. burkholderia pseudomallei resistant to antibiotics used for the treatment of melioidosis had been reported. the aim of this study was to determine the in vitro antibiotic susceptibility patterns of burkholderia pseudomallei isolated in malaysia to a panel of antibiotics used for the treatment of melioidosis and also to potential alternative antibiotics such as tigecycline, ampicillin/sulbacta ...201324194761
sequence-defined transposon mutant library of burkholderia thailandensis.we constructed a near-saturation transposon mutant library for burkholderia thailandensis, a low-virulence surrogate for the causative agent of melioidosis (burkholderia pseudomallei). a primary set of nearly 42,000 unique mutants (~7.5 mutants/gene) was generated using transposon tn5 derivatives. the strains carry insertions in 87% of the predicted protein-coding genes of the organism, corresponding to nearly all of those nonessential for growth on nutrient agar. to achieve high genome coverage ...201324194535
a case of mycotic aneurysm due to burkholderia pseudomallei.burkholderia pseudomallei is an free-living gram-negative bacterium causing melioidosis and is endemic in southeast asia. a 56-year-old diabetic construction worker with a 1-month history of abdominal pain and 1-day history of high-grade fever was found to have a left non-dissecting infrarenal mycotic aortic aneurysm by abdominal computerized tomography scan. bacteriological examination of his blood yielded burkholderia pseudomallei. the patient was treated with right axillo-bifemoral bypass wit ...201324353601
natural infection of burkholderia pseudomallei in an imported pigtail macaque (macaca nemestrina) and management of the exposed colony.identification of the select agent burkholderia pseudomallei in macaques imported into the united states is rare. a purpose-bred, 4.5-y-old pigtail macaque (macaca nemestrina) imported from southeast asia was received from a commercial vendor at our facility in march 2012. after the initial acclimation period of 5 to 7 d, physical examination of the macaque revealed a subcutaneous abscess that surrounded the right stifle joint. the wound was treated and resolved over 3 mo. in august 2012, 2 mo a ...201324326230
glibenclamide reduces pro-inflammatory cytokine production by neutrophils of diabetes patients in response to bacterial infection.type 2 diabetes mellitus is a major risk factor for melioidosis, which is caused by burkholderia pseudomallei. our previous study has shown that polymorphonuclear neutrophils (pmns) from diabetic subjects exhibited decreased functions in response to b. pseudomallei. here we investigated the mechanisms regulating cytokine secretion of pmns from diabetic patients which might contribute to patient susceptibility to bacterial infections. purified pmns from diabetic patients who had been treated with ...201324285369
correlates of immune protection following cutaneous immunization with an attenuated burkholderia pseudomallei vaccine.infections with the gram-negative bacterium burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with b. pseudomallei. at present, our understanding of what constitutes effective protective immunity against b. pseudomallei infection remains ...201324101688
discovery of inhibitors of burkholderia pseudomallei methionine aminopeptidase with antibacterial activity.evaluation of a series of metap inhibitors in an in vitro enzyme activity assay led to the first identification of potent molecules that show significant growth inhibition against burkholderia pseudomallei. nitroxoline analogs show excellent inhibition potency in the bpmetap1 enzyme activity assay with the lowest ic50 of 30 nm, and inhibit the growth of b. pseudomallei and b. thailandensis at concentrations ≥ 31 μm.201324376907
acute pulmonary melioidosis in a child: a case report and review of literature.melioidosis is a rare potentially fatal infection caused by the bacterium burkholderia pseudomallei, which is endemic in southeast asia and northern australia and an emerging pathogen in india. it is a largely under-diagnosed disease and an imitator of tuberculosis, both clinically and radiologically.201324604934
melioidosis :an emerging infection in india.melioidosis caused by the gram-negative bacterium burkholderia pseudomallei is endemic in southeast asia but may be under-diagnosed and under-reported in the indian subcontinent. this study was undertaken to analyse the clinical presentation and epidemiological risk factors for melioidosis in india.201324772696
disseminated melioidosis presenting as septic arthritis.melioidosis is an infection caused by burkholderia pseudomallei. the disease is known as a remarkable imitator due to the wide and variable clinical spectrum of its manifestations. septic arthritis is rare but well-recognized manifestation of this disease. we report a case of melioidosis in a 52 year male with uncontrolled diabetes mellitus (dm) presenting with a rare combination of septic arthritis and abscesses in the chest wall, liver and subcutaneous tissue. the patient responded to prolonge ...201223409422
an assessment of common marmoset (callithrix jacchus) γ9(+) t cells and their response to phosphoantigen in vitro.γ9δ2 t cells are a primate-specific γδ t cell subtype that expand and become activated during infection, responding directly to phosphoantigens which are by-products of essential metabolic pathways in both bacteria and mammals. analogues of natural phosphoantigens have been developed as potential immunotherapeutics for treatment of tumours and infectious diseases. several non-human primate models have been used in preclinical studies, however, little is known about marmoset γ9δ2 t cell responses ...201223399838
comparison of the efficiency of sampling devices for aerosolized burkholderia pseudomallei.previous studies have demonstrated that aerosol sampling devices can have deleterious effects on bacteria due to stresses intrinsic to the sampling processes. although a significant amount of work has been carried out to develop animal models of inhalational melioidosis, little information has been reported on the effects of the aerosol sampling devices on the causative bacterium, burkholderia pseudomallei. the aim of this study was to compare the efficiencies for collection of aerosolized bacte ...201222486343
[characterisation of burkholderia pseudomallei lethal factor 1 (blf1). a breakthrough against melioidosis]. 201222480647
burkholderia pseudomallei triggers altered inflammatory profiles in a whole-blood model of type 2 diabetes-melioidosis comorbidity.melioidosis is a potentially fatal disease caused by the bacterium burkholderia pseudomallei. type 2 diabetes (t2d) is the most common comorbidity associated with melioidosis. b. pseudomallei isolates from melioidosis patients with t2d are less virulent in animal models than those from patients with melioidosis and no identifiable risk factors. we developed an ex vivo whole-blood assay as a tool for comparison of early inflammatory profiles generated by t2d and nondiabetic (nd) individuals in re ...201222473609
ceftazidime resistance in burkholderia pseudomallei: first report from india.melioidosis, a disease of public health importance in southeast asia and northern australia, of late has shown an increasing trend in india, particularly southern india. we describe a case of a 39-year-old diabetic patient with left elbow septic arthritis, multiple liver, splenic abscesses, pneumonia, pleural effusion, followed by sepsis syndrome. blood cultures and culture of the joint aspirate yielded pure growth of burkholderia pseudomallei (b. pesudomallei), sensitive to carbapenem, co-trimo ...201222449529
construction and characterization of a burkholderia pseudomallei wzm deletion mutant.in burkholderia pseudomallei, the pathogen that causes melioidosis, the gene cluster encoding the capsular polysaccharide, is located on chromosome 1. among the 19 capsular genes in this cluster, wzm has not been thoroughly studied. to study the function of wzm, we generated a deletion mutant and compared it with the wild-type strain. the mutant produced less biofilm in minimal media and was more sensitive to desiccation and oxidative stress compared with the wild-type strain, indicating that wz ...201223075783
an objective approach for burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing.burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. no human vaccines are available that protect against b. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. although clinical trials could be used to test the efficacy of new medical countermeasures (mcms), the high mortality rates a ...201223057010
cranial melioidosis with extradural extension after a fall in the bathroom.a 32-year-old diabetic male, with a past history of head injury and seizures, presented with a painful swelling over his forehead present for the past three months. cranial mri demonstrated the presence of a scalp collection with extradural extension through a bony defect. biopsy from the area showed caseating necrosis suggestive of tuberculosis. although the patient failed to return for initiation of anti-tubercular therapy for the next 11 months, the swelling did not progress, and there were n ...201223024720
[study of extracellular antigens by immunodiffusion methods in differentiation of pathogenic burkholderiae].isolation and composition comparison of extracellular antigens (eca) of pathogenic burkholderiae in sds-page electrophoresis and their use for differentiation of these microorganisms by immunodiffusion methods.201222442972
comparison of taqman pcr assays for detection of the melioidosis agent burkholderia pseudomallei in clinical specimens.melioidosis is an emerging infectious disease caused by the soil bacterium burkholderia pseudomallei. in diagnostic and forensic settings, molecular detection assays need not only high sensitivity with low limits of detection but also high specificity. in a direct comparison of published and newly developed taqman pcr assays, we found the tts1-orf2 assay to be superior in detecting b. pseudomallei directly from clinical specimens. the ylf/btfc multiplex assay (targeting the yersinia-like fimbria ...201222442327
diffusion and activity of antibiotics against burkholderia pseudomallei biofilms.the diffusion and activity of ceftazidime (caz), imipenem (ipm) and trimethoprim/sulfamethoxazole (tmp/smx) against burkholderia pseudomallei biofilms were comparatively tested using the high biofilm-producing strain b. pseudomallei 377 and the biofilm-defective mutant b. pseudomallei m6. biofilms were generated by inoculation of bacteria on polycarbonate membranes placed on the surface of tryptic soy agar plates. the results showed that diffusion of tmp/smx through b. pseudomallei biofilms was ...201222364716
characterization of ceftazidime resistance mechanisms in clinical isolates of burkholderia pseudomallei from australia.burkholderia pseudomallei is a gram-negative bacterium that causes the serious human disease, melioidosis. there is no vaccine against melioidosis and it can be fatal if not treated with a specific antibiotic regimen, which typically includes the third-generation cephalosporin, ceftazidime (caz). there have been several resistance mechanisms described for b. pseudomallei, of which the best described are amino acid changes that alter substrate specificity in the highly conserved class a β-lactama ...201222363490
malleilactone, a polyketide synthase-derived virulence factor encoded by the cryptic secondary metabolome of burkholderia pseudomallei group pathogens.sequenced bacterial genomes are routinely found to contain gene clusters that are predicted to encode metabolites not seen in fermentation-based studies. pseudomallei group burkholderia are emerging pathogens whose genomes are particularly rich in cryptic natural product biosynthetic gene clusters. we systematically probed the influence of the cryptic secondary metabolome on the virulence of these bacteria and found that disruption of the mal gene cluster, which is natively silent in laboratory ...201222765305
neonatal melioidosis: systematic review of the literature.twenty-two cases of neonatal melioidosis were identified with the primary outcome from a systematic review, and the clinical presentations were either bacteremia and/or meningitis with burkholderia pseudomallei isolated in all cases. ten cases reported the mode of transmission: infections that occurred from mother-to-child transmission (20%), and infections that were probably healthcare-associated (40%) and community-acquired (40%). the crude mortality was 73% (16/22).201222739573
neutrophil extracellular traps exhibit antibacterial activity against burkholderia pseudomallei and are influenced by bacterial and host factors.burkholderia pseudomallei is the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. polymorphonuclear neutrophils (pmns) kill microbes extracellularly by the release of neutrophil extracellular traps (nets). pmns play a key role in the control of melioidosis, but the involvement of nets in killing of b. pseudomallei remains obscure. here, we showed that bactericidal nets were released from human pmns in response to b. pseudomallei in a dose- and time-de ...201222927051
regulation of a quorum sensing system by stationary phase sigma factor rpos and their co-regulation of target genes in burkholderia pseudomallei.burkholderia pseudomallei is the causative agent of a fatal disease, melioidosis. however, the mechanisms of pathogenesis and genes involved in its virulence are not understood. in the current study, whether stationary phase and stress response sigma factor rpos and bpsi-mediated quorum sensing (qs) system co-regulate its target genes was investigated. positive regulation of rpos on bpsi expression and autoinducer production in stationary phase, but not on flic and ppk expression, was observed. ...201222385268
severe coinfection of melioidosis and dengue fever in northeastern brazil: first case report.this report focuses on a fatality involving severe dengue fever and melioidosis in a 28-year-old truck driver residing in pacoti in northeastern brazil. he exhibited long-term respiratory symptoms (48 days) and went through a wide-ranging clinical investigation at three hospitals, after initial clinical diagnoses of pneumonia, visceral leishmaniasis, tuberculosis, and fungal sepsis. after death, burkholderia pseudomallei was isolated in a culture of ascitic fluid. dengue virus type 1 was detecte ...201222370846
differential host response to burkholderia pseudomallei: tissue plasminogen activator*. 201222710226
genomic islands as a marker to differentiate between clinical and environmental burkholderia pseudomallei.burkholderia pseudomallei, as a saprophytic bacterium that can cause a severe sepsis disease named melioidosis, has preserved several extra genes in its genome for survival. the sequenced genome of the organism showed high diversity contributed mainly from genomic islands (gis). comparative genome hybridization (cgh) of 3 clinical and 2 environmental isolates, using whole genome microarrays based on b. pseudomallei k96243 genes, revealed a difference in the presence of genomic islands between cl ...201222675491
use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis for rapid confirmation of burkholderia pseudomallei in septicemic melioidosis.burkholderia pseudomallei was quickly identified from blood cultures collected from septicemic patients by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis using an in-house reference library. this procedure reduced the time to definitive identification by more than 24 hours. this analysis is a useful addition to laboratory methods for early recognition of septicemic melioidosis in non-endemic settings.201222665614
workshop on treatment of and postexposure prophylaxis for burkholderia pseudomallei and b. mallei infection, 2010.the us public health emergency medical countermeasures enterprise convened subject matter experts at the 2010 hhs burkholderia workshop to develop consensus recommendations for postexposure prophylaxis against and treatment for burkholderia pseudomallei and b. mallei infections, which cause melioidosis and glanders, respectively. drugs recommended by consensus of the participants are ceftazidime or meropenem for initial intensive therapy, and trimethoprim/sulfamethoxazole or amoxicillin/clavulan ...201223171644
tn5-ot182 should not be used to identify genes involved in biofilm formation in burkholderia pseudomallei.burkholderia pseudomallei, a gram-negative bacterium, is the causative agent of melioidosis. one of the important virulence properties of this bacteria is its ability to form a biofilm. genes involved in biofilm formation in b. pseudomallei have not been thoroughly studied. in this study, tn5-ot182 mutagenesis was used to isolate of b. pseudomallei strain a2 mutants unable to produce biofilm. ten biofilm-defective transposon mutants were isolated and analyzed. flanking dna from each transposon m ...201223082562
case cluster shifting and contaminant source as determinants of melioidosis in taiwan.to assess the geographical distribution of melioidosis contamination sources and the association between the location of melioidosis cases and positive sampling sites for burkholderia pseudomallei in taiwan.201222809327
development of a diagnostic system for burkholderia pseudomallei infections.monoclonal antibodies were generated against whole cell lysate of burkholderia pseudomallei. two out of 6 monoclonal antibodies were found specific and exhibited high affinity against b. pseudomallei, one of which, was utilized to develop sandwich elisa for detection of specific b. pseudomallei antigen. immunoassays were found to be specific as no reaction was observed with closely related burkholderia and pseudomonas species. blood samples from experimentally infected mice were found positive f ...201222806151
evaluation of six commercial dna extraction kits for recovery of burkholderia pseudomallei dna.six commercially available dna extraction kits, as well as thermal lysis and proteinase k dna extraction were evaluated regarding bacterial inactivation, dna yield and purity, and their use in a burkholderia pseudomallei real-time pcr. while all methods successfully inactivated the bacteria, by measuring dna purity and the level of detection by real-time pcr, the proteinase k method was the most sensitive.201223022447
transverse myelitis secondary to melioidosis: a case report.melioidosis has become an emerging infection in sri lanka; a country which is considered non endemic for it. paraplegia due to burkholderia pseudomallei is a very rare entity encountered even in countries where the disease is endemic. there are no reported cases of transverse myelitis due to melioidosis in sri lankan population thus we report the first case.201223020820
matrix-assisted laser desorption ionization-time of flight mass spectrometry for rapid identification of burkholderia pseudomallei: importance of expanding databases with pathogens endemic to different localities. 201222718946
glycogen synthase kinase-3β inhibition improved survivability of mice infected with burkholderia pseudomallei.the disease melioidosis, caused by the soil bacteria burkholderia pseudomallei, often manifests as acute septicemia with high fatality. glycogen synthase kinase-3β (gsk3β) plays a key role during the inflammatory response induced by bacteria. we used a murine model of acute melioidosis to investigate the effects of licl, a gsk3 inhibitor on experimental animal survivability as well as tnf-α, il-1β, ifn-γ, il-10 and il-1ra cytokine levels in blood, lung, liver and spleen of b. pseudomallei-infect ...201223202600
development and characterization of a caprine aerosol infection model of melioidosis.infection with burkholderia pseudomallei causes the disease melioidosis, which often presents as a serious suppurative infection that is typically fatal without intensive treatment and is a significant emerging infectious disease in southeast asia. despite intensive research there is still much that remains unknown about melioidosis pathogenesis. new animal models of melioidosis are needed to examine novel aspects of pathogenesis as well as for the evaluation of novel therapeutics. the objective ...201222916225
burkholderia pseudomallei osteomyelitis: an unusual cause of fever in a returned traveller.a 52-year-old diabetic man presented to the emergency department with a history of fevers and pain in his right thigh. he had recently returned from a 10-month trip to vietnam. a suspected bacterial abscess in the right thigh did not respond to empirical antibiotics. subsequent investigations revealed melioidotic osteomyelitis of the femur. this case emphasises the need to consider the diagnosis of melioidosis in patients presenting with fever following travel in endemic areas.201222905056
persistent gastric colonization with burkholderia pseudomallei and dissemination from the gastrointestinal tract following mucosal inoculation of mice.melioidosis is a disease of humans caused by opportunistic infection with the soil and water bacterium burkholderia pseudomallei. melioidosis can manifest as an acute, overwhelming infection or as a chronic, recurrent infection. at present, it is not clear where b. pseudomallei resides in the mammalian host during the chronic, recurrent phase of infection. to address this question, we developed a mouse low-dose mucosal challenge model of chronic b. pseudomallei infection and investigated sites o ...201222624016
endogenous tissue-type plasminogen activator impairs host defense during severe experimental gram-negative sepsis (melioidosis)*.melioidosis is a frequent cause of severe sepsis in southeast asia caused by the gram-negative bacterium burkholderia pseudomallei. patients with melioidosis have elevated circulating levels of tissue-type plasminogen activator, an important regulator of fibrinolysis. in this study, we aimed to investigate the role of tissue-type plasminogen activator during melioidosis.201222564963
burkholderia pseudomallei detection in surface water in southern laos using moore's swabs.the causal agent of melioidosis, burkholderia pseudomallei, has been cultured from paddy fields in the lao pdr. we carried out a pilot study to examine the relationship between bacterial soil contamination and that of nearby surface waters in saravane province. soil sampling was conducted at a depth of 30 cm (100 holes in a 45 × 45 m grid) at two sites, east and west saravane. moore's swabs were used for water sampling of paddy fields, lakes, rivers, boreholes, and storage tanks within 2 km of t ...201222556090
crystallization and preliminary x-ray analysis of the receiver domain of a putative response regulator, bpsl0128, from burkholderia pseudomallei.bpsl0128, a gene encoding a putative response regulator from burkholderia pseudomallei strain d286, has been cloned into a petblue-1 vector system, overexpressed in escherichia coli and purified. the full-length protein is degraded during purification to leave a fragment corresponding to the putative receiver domain, and crystals of this protein that diffracted to beyond 1.75 å resolution have been grown by the hanging-drop vapour-diffusion technique using peg 6000 as the precipitant. the crysta ...201222869122
molecular investigation of virulence determinants between a virulent clinical strain and an attenuated strain of burkholderia pseudomallei.burkholderia pseudomallei is the causative agent of melioidosis. we initiated this investigation with a virulent and an attenuated strain of b. pseudomallei. pulsed-field gel electrophoresis was carried out initially for macrogenomic comparison of both strains of b. pseudomallei. however, the pulsotypes obtained were identical and therefore we applied a subtractive hybridization technique to distinguish and determine the possible differences between the two strains. six virulence strain-specific ...201222846664
blf1, the first burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.melioidosis is a disease caused by infection with burkholderia pseudomallei. the molecular basis for the pathogenicity of b. pseudomallei is poorly understood. however, recent work has identified the first toxin from this bacterium and shown that it inhibits host protein synthesis. here, we review the illness that is potentially associated with biological warfare, the pathogen and its deadly molecular mechanism of action, as well as therapeutic developments that may follow.201222817745
first genome sequence of a burkholderia pseudomallei isolate in china, strain bpc006, obtained from a melioidosis patient in hainan.melioidosis, caused by burkholderia pseudomallei, is considered to be endemic to northern australia and southeast asia, with high mortality and relapse rates, regardless of powerful antibiotic therapy. here we report the first genome sequence of burkholderia pseudomallei strain bpc006, obtained from a melioidosis patient in hainan, china. the genome sizes of the 2 chromosomes were determined to be 4,001,777 bp and 3,153,284 bp.201223144371
murine pulmonary infection and inflammation induced by inhalation of burkholderia pseudomallei.melioidosis is a tropical disease caused by ingestion, percutaneous inoculation or inhalation of the gram-negative soil saprophyte burkholderia pseudomallei. we developed a reproducible experimental murine model of pneumonic melioidosis induced by inhalation of aerosolized b. pseudomallei 1026b. in a series of experiments performed to bracket the lethal dose, we found that c57bl/6 mice were modestly more resistant than balb/c mice (median lethal dose 334 cfu/lung vs 204 cfu/lung). we further cha ...201223136994
detection of burkholderia pseudomallei o-antigen serotypes in near-neighbor species.burkholderia pseudomallei is the etiological agent of melioidosis and a cdc category b select agent with no available effective vaccine. previous immunizations in mice have utilized the lipopolysaccharide (lps) as a potential vaccine target because it is known as one of the most important antigenic epitopes in b. pseudomallei. complicating this strategy are the four different b. pseudomallei lps o-antigen types: a, b, b2, and rough. sero-crossreactivity is common among o-antigens of burkholderia ...201223126230
expression and characterization of an iron-containing superoxide dismutase from burkholderia pseudomallei.a superoxide dismutase (sod) gene from burkholderia pseudomallei, the causative agent of melioidosis, was cloned and expressed in escherichia coli, and its product was functionally and physically characterized. the gene has an open-reading frame of 579 bp. the deduced amino acid sequence has 192 residues with a calculated molecular mass of ~22 kda. sequence comparison with other bacterial sods showed that the protein contains typical metal-binding motifs and other fe-sod-conserved residues. the ...201223274991
φx216, a p2-like bacteriophage with broad burkholderia pseudomallei and b. mallei strain infectivity.burkholderia pseudomallei and b. mallei are closely related category b select agents of bioterrorism and the causative agents of the diseases melioidosis and glanders, respectively. rapid phage-based diagnostic tools would greatly benefit early recognition and treatment of these diseases. there is extensive strain-to-strain variation in b. pseudomallei genome content due in part to the presence or absence of integrated prophages. several phages have previously been isolated from b. pseudomallei ...201223217012
outbreak of melioidosis and leptospirosis co-infection following a rescue operation.we analyzed the epidemiological data of all people who were involved in the search and rescue operation in lubuk yu, a natural recreational forest with waterfall and stream. the hospital admission records of the cases who fulfilled the case definition and the environmental samples result taken at lubuk yu recreational area were studied. 153 people were exposed to this outbreak, 85 (55.5%) were professional rescuers from various government agencies and 68 (44.5%) were villagers. 21 fulfilled the ...201223082420
burkholderia pseudomallei kills caenorhabditis elegans through virulence mechanisms distinct from intestinal lumen colonization.the nematode caenorhabditis elegans is hypersusceptible to burkholderia pseudomallei infection. however, the virulence mechanisms underlying rapid lethality of c. elegans upon b. pseudomallei infection remain poorly defined. to probe the host-pathogen interaction, we constructed gfp-tagged b. pseudomallei and followed bacterial accumulation within the c. elegans intestinal lumen. contrary to slow-killing by most bacterial pathogens, b. pseudomallei caused fairly limited intestinal lumen coloniza ...201223076282
structural mechanism of ubiquitin and nedd8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.targeting eukaryotic proteins for deamidation modification is increasingly appreciated as a general bacterial virulence mechanism. here, we present an atomic view of how a bacterial deamidase effector, cycle-inhibiting factor homolog in burkholderia pseudomallei (chbp), recognizes its host targets, ubiquitin (ub) and ub-like neural precursor cell expressed, developmentally down-regulated 8 (nedd8), and catalyzes site-specific deamidation. crystal structures of chbp-ub/nedd8 complexes show that u ...201223175788
intoxication vs. infection: a decade of studying burkholderia pseudomallei virulence in a simple infection model. 201223211680
involvement of signal regulatory protein α, a negative regulator of toll-like receptor signaling, in impairing the myd88-independent pathway and intracellular killing of burkholderia pseudomallei-infected mouse macrophages.the facultative intracellular gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis and is known for its ability to evade the toll-like receptor (tlr)-mediated innate immune response. previously it has been demonstrated that this bacterium was able to suppress the myd88-independent pathway and can survive macrophage intracellular killing. however, the underlying mechanisms responsible for the suppression of this pathway are not fully understood. in the present s ...201222988019
development of ceftazidime resistance in an acute burkholderia pseudomallei infection.burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. first-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (caz), as almost all b. pseudomallei strains are susceptible to this drug. however, acquired caz resistance can develop in vivo during treatment with caz, which can lead to mortality if therapy is not switched to a different drug in a timely manner. serial b. pseudomallei i ...201222977307
a preliminary x-ray study of transketolase from burkholderia pseudomallei.tkta is the most critical enzyme in the nonoxidative pentose phosphate pathway. it catalyzes the conversion of xylulose 5-phosphate and ribose 5-phosphate into sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate, and its products are used in the biosynthesis of acetyl-coa, aromatic amino acids, nucleic acids and adp-l-glycero-β-d-manno-heptose. tkta also has an unexpected role in chromosome structure that is independent of its metabolic responsibilities. therefore, it is a new potent antibi ...201223192046
nitric oxide-dependent killing of aerobic, anaerobic and persistent burkholderia pseudomallei.burkholderia pseudomallei infections are fastidious to treat with conventional antibiotic therapy, often involving a combination of drugs and long-term regimes. bacterial genetic determinants contribute to the resistance of b. pseudomallei to many classes of antibiotics. in addition, anaerobiosis and hypoxia in abscesses typical of melioidosis select for persistent populations of b. pseudomallei refractory to a broad spectrum of antibacterials. we tested the susceptibility of b. pseudomallei to ...201222521523
emerging clinico-epidemiological trends in melioidosis: analysis of 95 cases from western coastal india.to study the clinico-epidemiological trends in melioidosis, an emerging disease in the western coastal region of india.201222512851
seroepidemiological surveillance of burkholderia pseudomallei in bangladesh.melioidosis (burkholderia pseudomallei infection) has yet to be demonstrated systematically in bangladesh. a prospective, cross-sectional serological survey was conducted in 2010 at six bangladeshi hospitals. age, gender, occupation and residential address were recorded. of 1244 patients, 359 (28.9%) were positive for b. pseudomallei by indirect haemagglutination assay. farmers had an increased risk of seropositivity (risk ratio=1.4, 95% ci 1.0-1.8; p=0.03). there was no clear geographic cluster ...201222795754
development of hydrolysis probe-based real-time pcr for identification of virulent gene targets of burkholderia pseudomallei and b. mallei--a retrospective study on archival cases of service members with melioidosis and glanders.burkholderia pseudomallei and b. mallei are two highly pathogenic bacteria responsible for melioidosis and glanders, respectively. our laboratory developed hydrolysis probe-based real-time polymerase chain reaction assays targeting type three secretion system (tts) and transposase family protein (tfp) of b. pseudomallei and b. malli, respectively. the assays were validated for target specificity, amplification sensitivity, and reproducibility. a bacterial dna panel, composed of b. pseudomallei ( ...201222360070
validation of a burkholderia pseudomallei hypothetical protein and determination of its translational start codon using chromosomal integration of his-tag coding sequence.in this post genomic era, there are a great number of in silico annotated hypothetical genes. however, experimental validation of the functionality of these genes remains tentative. two of the major challenges faced by researcher are whether these hypothetical genes are protein-coding genes and whether their corresponding predicted translational start codons are correct. in this report, we demonstrate a convenient procedure to validate the presence of a hypothetical gene product of bpss1356 from ...201222354666
development and validation of burkholderia pseudomallei-specific real-time pcr assays for clinical, environmental or forensic detection applications.the bacterium burkholderia pseudomallei causes melioidosis, a rare but serious illness that can be fatal if untreated or misdiagnosed. species-specific pcr assays provide a technically simple method for differentiating b. pseudomallei from near-neighbor species. however, substantial genetic diversity and high levels of recombination within this species reduce the likelihood that molecular signatures will differentiate all b. pseudomallei from other burkholderiaceae. currently available molecular ...201222624061
melioidosis vaccines: a systematic review and appraisal of the potential to exploit biodefense vaccines for public health purposes.burkholderia pseudomallei is a category b select agent and the cause of melioidosis. research funding for vaccine development has largely considered protection within the biothreat context, but the resulting vaccines could be applicable to populations who are at risk of naturally acquired melioidosis. here, we discuss target populations for vaccination, consider the cost-benefit of different vaccination strategies and review potential vaccine candidates.201222303489
interaction of burkholderia pseudomallei and burkholderia thailandensis with human monocyte-derived dendritic cells.burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic in areas of south-east asia and northern australia, and is classed as a category b select agent by the centers for disease control and prevention (cdc). factors that determine whether host infection is achieved or if disease is chronic or acute are unknown but the type of host immune response that is mounted is important. b. pseudomallei can replicate within macrophages, causing them to multinucleate. in light of ...201222301613
pediatric suppurative parotitis in cambodia between 2007 and 2011.the causes of suppurative parotitis in cambodian children are not known. we describe 39 cases at the angkor hospital for children, siem reap, between january 2007 and july 2011 (0.07/1000 hospital attendances). the median age was 5.7 years with no neonates affected. burkholderia pseudomallei was cultured in 29 (74%) cases. no deaths occurred; 1 child developed facial nerve palsy.201222531239
polysaccharide specific monoclonal antibodies provide passive protection against intranasal challenge with burkholderia pseudomallei.burkholderia pseudomallei is a gram-negative bacillus that is the causative agent of melioidosis. the bacterium is inherently resistant to many antibiotics and mortality rates remain high in endemic areas. the lipopolysaccharide (lps) and capsular polysaccharide (cps) are two surface-associated antigens that contribute to pathogenesis. we previously developed two monoclonal antibodies (mabs) specific to the cps and lps; the cps mab was shown to identify antigen in serum and urine from melioidosi ...201222530013
dna binding site analysis of burkholderia thailandensis response regulators.bacterial response regulators (rr) that function as transcription factors in two component signaling pathways are crucial for ensuring tight regulation and coordinated expression of the genome. currently, consensus dna binding sites in the promoter for very few bacterial rrs have been identified. a systematic method to characterize these dna binding sites for rrs would enable prediction of specific gene expression patterns in response to extracellular stimuli. to identify rr dna binding sites, w ...201222521922
sesquiterpene farnesol contributes to increased susceptibility to β-lactams in strains of burkholderia pseudomallei.this study aimed to evaluate the in vitro combination of farnesol and β-lactams against burkholderia pseudomallei. a total of 12 β-lactamase-positive strains were tested according to clsi standards. all strains were inhibited by farnesol, with mics ranging from 75 to 150 μm. the combination of this compound with β-lactams resulted in statistically significant β-lactam mic reduction (p ≤ 0.05). this study provides new perspectives for the use of farnesol combined with β-lactam antibiotics against ...201222290941
melioidosis presenting with mediastinal lymphadenopathy masquerading as malignancy: a case report.melioidosis, endemic in thailand and in the northern territory of australia is an emerging infectious disease in india which can present with varied forms. a case of melioidosis, presenting as a rare anterior mediastinal mass which can masquerade as malignancy or tuberculosis, is described here. with treatment, our patient initially showed an increase in the size of mediastinal node and development of new submandibular node.. to the best of our knowledge, this phenomenon has not been documented ...201222269609
melioidosis--an uncommon but also under-recognized cause of pneumonia in papua new guinea.melioidosis is being increasingly recognized as an important cause of severe, acute community-acquired pneumonia in various tropical regions. the chronic form of melioidosis can also mimic tuberculosis. studies have established that, while uncommon in the port moresby region, melioidosis is an important cause of pneumonia and sepsis in the balimo region of western province. phylogenetic analyses of strains of burkholderia pseudomallei from papua new guinea have shown them to be more closely rela ...201223163189
glutathione deficiency in type 2 diabetes impairs cytokine responses and control of intracellular bacteria.individuals with type 2 diabetes are at increased risk of acquiring melioidosis, a disease caused by burkholderia pseudomallei infection. although up to half of melioidosis patients have underlying diabetes, the mechanisms involved in this increased susceptibility are unknown. we found that b. pseudomallei-infected pbmcs from diabetic patients were impaired in il-12p70 production, which resulted in decreased ifn-γ induction and poor bacterial killing. the defect was specific to the il-12-ifn-γ a ...201222546856
enzymatic profiling of clinical and environmental isolates of burkholderia pseudomallei.melioidosis has been recognized as an important cause of sepsis in the tropics. the disease caused by an environmental saprophyte burkholderia pseudomallei, affects mostly adults with underlying immunocompromised conditions. in this study, the enzymatic profiles of 91 clinical and 9 environmental isolates of b. pseudomallei were evaluated using the apizym system, in addition to assessment of protease, phospholipase c and sialidase activities using agar plate methods and other assays. the activit ...201222543616
distinct human antibody response to the biological warfare agent burkholderia mallei.the genetic similarity between burkholderia mallei (glanders) and burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. in 2000, the first human case of glanders in north america since 1945 was reported in a microbiology laboratory worker. leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohor ...201223076276
development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders.burkholderia pseudomallei and burkholderia mallei, the etiologic agents of melioidosis and glanders, respectively, cause severe disease in humans and animals and are considered potential agents of biological warfare and terrorism. diagnosis and treatment of infections caused by these pathogens can be challenging and, in the absence of chemotherapeutic intervention, acute disease is frequently fatal. at present, there are no human or veterinary vaccines available for immunization against these em ...201222912938
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