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comprehensive identification of virulence factors required for respiratory melioidosis using tn-seq mutagenesis.respiratory melioidosis is a disease presentation of the biodefense pathogen, burkholderia pseudomallei, which is frequently associated with a lethal septicemic spread of the bacteria. we have recently developed an improved respiratory melioidosis model to study the pathogenesis of burkholderia pseudomallei in the lung (intubation-mediated intratracheal [imit] inoculation), which more closely models descriptions of human melioidosis, including prominent septicemic spread from the lung and reduce ...201526583079
functional and structural characterization of a heparanase.we report the structural and functional characterization of a novel heparanase (bphep) from the invasive pathogenic bacterium burkholderia pseudomallei (bp), showing ∼24% sequence identity with human heparanase (hhep). site-directed mutagenesis studies confirmed the active site resi-dues essential for activity, and we found that bphep has specificity for heparan sulfate. finally, we describe the first heparanase x-ray crystal structure, which provides new insight into both substrate recognition ...201526565989
burkholderia pseudomallei induces il-23 production in primary human monocytes.burkholderia pseudomallei, a gram-negative intracellular bacterium, is a causative agent of melioidosis. the bacterium has been shown to induce the innate immune response, particularly pro-inflammatory cytokine production in several of both mouse and human cell types. in the present study, we investigate host immune response in b. pseudomallei-infected primary human monocytes. we discover that wild-type b. pseudomallei is able to survive and multiply inside the primary human monocytes. in contra ...201626563410
characterization of the murine macrophage response to infection with virulent and avirulent burkholderia species.burkholderia pseudomallei (bp) and burkholderia mallei (bm) are gram-negative facultative intracellular pathogens, which are the causative agents of melioidosis and glanders, respectively. depending on the route of exposure, aerosol or transcutaneous, infection by bp or bm can result in an extensive range of disease - from acute to chronic, relapsing illness to fatal septicemia. both diseases are associated with difficult diagnosis and high fatality rates. about ninety five percent of patients s ...201526545875
melioidosis in new caledonia: a dominant strain in a transmission hotspot.melioidosis is an infectious disease caused by burkholderia pseudomallei, a bacterium endemic in southeast asia and northern australia. in new caledonia, sporadic cases were first described in 2005; since then, more cases have been identified. to improve our understanding of melioidosis epidemiology in new caledonia, we compared the local cases and b. pseudomallei isolates with those from endemic areas. nineteen melioidosis cases have been diagnosed in new caledonia since 1999, mostly severe and ...201626542622
selecting soluble/foldable protein domains through single-gene or genomic orf filtering: structure of the head domain of burkholderia pseudomallei antigen bpsl2063.the 1.8 å resolution crystal structure of a conserved domain of the potential burkholderia pseudomallei antigen and trimeric autotransporter bpsl2063 is presented as a structural vaccinology target for melioidosis vaccine development. since bpsl2063 (1090 amino acids) hosts only one conserved domain, and the expression/purification of the full-length protein proved to be problematic, a domain-filtering library was generated using β-lactamase as a reporter gene to select further bpsl2063 domains. ...201526527140
burkholderia pseudomallei genotype distribution in the northern territory, australia.melioidosis is a tropical disease of high mortality caused by the environmental bacterium, burkholderia pseudomallei. we have collected clinical isolates from the highly endemic northern territory of australia routinely since 1989, and animal and environmental b. pseudomallei isolates since 1991. here we provide a complete record of all b. pseudomallei multilocus sequence types (sts) found in the northern territory to date, and distribution maps of the eight most common environmental sts. we obs ...201626526925
the contribution of soil physicochemical properties to the presence and genetic diversity of burkholderia pseudomallei.burkholderia pseudomallei (bp), the causative agent of melioidosis, is unevenly distributed in the complex soil environment. physicochemical factors in the soil have been reported to affect microbial communities in the soil. the effect of physicochemical factors on the number and diversity of organisms in the soil has not been reported. twenty-five each b. pseudomallei-positive and -negative soil samples were collected from a melioidosis-endemic area. the amount of bp in each soil sample was mea ...201526513904
a pcr-based detection of burkholderia pseudomallei diversity using myoviridae prophage typing.pcr-based detection of myoviridae lysogenic phages in burkholderia pseudomallei was developed using primers targeting k96243 prophage gi2, phie12-2 and phi52237/phix216. investigation of 50 clinical and 50 environmental (soil) isolates revealed that k96243 prophage gi2 was the most common (48%) among the isolates, followed by phie12-2 (38%) and phi52237/phix216 (35%), with k96243 prophage gi2 being significantly more frequent in soil (64%) than clinical (32%) samples. twenty-four percent of soil ...201526513903
t-cell responses are associated with survival in acute melioidosis patients.melioidosis is an increasingly recognised cause of sepsis and death across south east asia and northern australia, caused by the bacterium burkholderia pseudomallei. risk factors include diabetes, alcoholism and renal disease, and a vaccine targeting at-risk populations is urgently required. a better understanding of the protective immune response in naturally infected patients is essential for vaccine design.201526495852
central and peripheral nervous system involvement in neuromelioidosis.we report a case of a 33-year-old sri lankan man who presented with flaccid quadriparesis with brainstem signs and acute motor axonal polyneuropathy. mri of the brain showed multiple abscesses with ring enhancement seen predominantly in the brainstem and upper cervical cord. the patient was initially treated with intravenous immunoglobulin, considering this to be a form of guillain-barré syndrome. cerebrospinal fluid, however, showed lymphocytic pleocytosis with raised protein. tests for brucell ...201526494715
use of whole-genome sequencing to link burkholderia pseudomallei from air sampling to mediastinal melioidosis, australia.the frequency with which melioidosis results from inhalation rather than percutaneous inoculation or ingestion is unknown. we recovered burkholderia pseudomallei from air samples at the residence of a patient with presumptive inhalational melioidosis and used whole-genome sequencing to link the environmental bacteria to b. pseudomallei recovered from the patient.201526488732
correlation between biofilm production, antibiotic susceptibility and exopolysaccharide composition in burkholderia pseudomallei bpsi, ppk, and rpos mutant strains.burkholderia pseudomallei is the cause of melioidosis, a fatal tropical infectious disease, which has been reported to have a high rate of recurrence, even when an intensive dose of antibiotics is used. biofilm formation is believed to be one of the possible causes of relapse because of its ability to increase drug resistance. eps in biofilms have been reported to be related to the limitation of antibiotic penetration in b. pseudomallei. however, the mechanisms by which biofilms restrict the dif ...201526486518
pangenome analysis of burkholderia pseudomallei: genome evolution preserves gene order despite high recombination rates.the pangenomic diversity in burkholderia pseudomallei is high, with approximately 5.8% of the genome consisting of genomic islands. genomic islands are known hotspots for recombination driven primarily by site-specific recombination associated with trnas. however, recombination rates in other portions of the genome are also high, a feature we expected to disrupt gene order. we analyzed the pangenome of 37 isolates of b. pseudomallei and demonstrate that the pangenome is 'open', with approximatel ...201526484663
comparison of whole-genome sequences from two colony morphovars of burkholderia pseudomallei.the entire genomes of two isogenic morphovars (vgh16w and vgh16r) of burkholderia pseudomallei were sequenced. a comparison of the sequences from both strains indicates that they show 99.99% identity, are composed of 22 tandem repeated sequences with <100 bp of indels, and have 199 single-base variants.201526472836
draft genome sequence of burkholderia pseudomallei strain 350105, isolated in hainan, china, in 1976.burkholderia pseudomallei is the etiological agent of the potentially fatal disease melioidosis. here, we report the draft genome sequence of a virulent water isolate obtained from the hainan province of china in 1976, b. pseudomallei strain 350105.201526472827
lytic capability of bacteriophages (family myoviridae) on burkholderia pseudomallei.burkholderia pseudomallei, a gram-negative bacillus found in soil and water, is the causative agent of melioidosis. it can produce a biofilm, which increases resistance to antibacterial agents. bacteriophages (phages) have been suggested as alternative antibacterial agents. in this study, the ability of six phages (family myoviridae) to lyse b. pseudomallei isolates was examined using a microplate phage virulence assay. the six phages were more efficient in lysing soil than clinical b. pseudomal ...201426466420
a review of melioidosis cases in the americas.melioidosis is a bacterial infection caused by burkholderia pseudomallei, a gram-negative saprophytic bacillus. cases occur sporadically in the americas with an increasing number of cases observed among people with no travel history to endemic countries. to better understand the incidence of the disease in the americas, we reviewed the literature, including unpublished cases reported to the centers for disease control and prevention. of 120 identified human cases, occurring between 1947 and june ...201526458779
emergence of melioidosis in indonesia.melioidosis is known to be highly endemic in parts of southeast asia and northern australia; however, cases are rarely reported in indonesia. here we report three cases of melioidosis in makassar, south sulawesi, indonesia occurring between 2013 and 2014. two patients died and the other was lost to follow-up. burkholderia pseudomallei isolates from all three cases were identified by the vitek2 compact installed in the hospital in 2012. none of the three patients reported received antimicrobials ...201526458777
an international, multicentre evaluation and description of burkholderia pseudomallei infection in cystic fibrosis.several cases of burkholderia pseudomallei infection in cf have been previously reported. we aimed to identify all cases globally, risk factors for acquisition, clinical consequences, and optimal treatment strategies.201526453341
draft genome sequences of burkholderia pseudomallei and staphylococcus aureus, isolated from a patient with chronic rhinosinusitis.here, we report the draft genome sequences of burkholderia pseudomallei and staphylococcus aureus causing chronic rhinosinusitis. whole-genome sequencing determined the b. pseudomallei as sequence type (st) 1381 and the s. aureus as st8. b. pseudomallei possessed the blaoxa-59 gene. this study illustrates the potential emergence of b. pseudomallei in cases of chronic rhinosinusitis.201526430027
evaluation of a biodegradable microparticulate polymer as a carrier for burkholderia pseudomallei subunit vaccines in a mouse model of melioidosis.melioidosis, a potentially lethal disease of humans and animals, is caused by the soil-dwelling bacterium burkholderia pseudomallei. due to b. pseudomallei's classification as a tier 1 select agent, there is substantial interest in the development of an effective vaccine. yet, despite decades of research, no effective target, adjuvant or delivery vehicle capable of inducing protective immunity against b. pseudomallei infection has been identified. we propose a microparticulate delivery vehicle c ...201526428631
association between activities related to routes of infection and clinical manifestations of melioidosis.we sought associations between route of infection by burkholderia pseudomallei and clinical manifestations in 330 cases of melioidosis in northeast thailand using bivariate multivariable logistic regression models. activities related to skin inoculation were negatively associated with bacteraemia, activities related to ingestion were associated with bacteraemia, and activities related to inhalation were associated with pneumonia. our study suggests that route of infection is one of the factors r ...201626417852
brief communication genotyping of burkholderia pseudomallei revealed high genetic variability among isolates from a single population group.burkholderia pseudomallei is a soil dwelling gram-negative bacteria predominates in southeast asia zone and the tropical part of australia. genetic diversity has been explored among various populations and environments worldwide. to date, little data is available on mlst profiling of clinical b. pseudomallei isolates in peninsular malaysia. in this brief report, thirteen culture positive b. pseudomallei cases collected from a single population of terengganu state in the western peninsular malays ...201526417404
burkholderia pseudomallei infection in us traveler returning from mexico, 2014. 201526401597
environmental attributes influencing the distribution of burkholderia pseudomallei in northern australia.factors responsible for the spatial and temporal clustering of burkholderia pseudomallei in the environment remain to be elucidated. whilst laboratory based experiments have been performed to analyse survival of the organism in various soil types, such approaches are strongly influenced by alterations to the soil micro ecology during soil sanitisation and translocation. during the monsoonal season in townsville, australia, b. pseudomallei is discharged from castle hill (an area with a very high ...201526398904
melioidosis as a travel-associated infection: case report and review of the literature.increasing numbers of sporadic cases of melioidosis in returning travelers have been reported from non-endemic regions.201526385170
unusual presentation of melioidosis in a case of pseudoaneurysm of descending thoracic aorta: review of two case reports.melioidosis is a rapidly fatal infectious disease caused by burkholderia pseudomallei, an agent of potential biothreat, endemic in several parts of india. most melioidosis-induced infected aneurysms are located in the abdominal or thoracic aorta.201526380820
gipsy: genomic island prediction software.bacteria are highly diverse organisms that are able to adapt to a broad range of environments and hosts due to their high genomic plasticity. horizontal gene transfer plays a pivotal role in this genome plasticity and in evolution by leaps through the incorporation of large blocks of genome sequences, ordinarily known as genomic islands (geis). geis may harbor genes encoding virulence, metabolism, antibiotic resistance and symbiosis-related functions, namely pathogenicity islands (pais), metabol ...201626376473
synthesis of the tetrasaccharide repeating unit of the β-kdo-containing exopolysaccharide from burkholderia pseudomallei and b. cepacia complex.the synthesis of the repeating unit of the immunogenic β-kdo-containing exopolysaccharide produced by burkholderia pseudomallei and bacteria of the b. cepacia complex is described. the target tetrasaccharide was synthesized via stereoselective 1,2-cis- and 1,2-trans-galactosylations and β-kdosylation. a [3 + 1] coupling reaction between a trigalactosyl n-phenyl-2,2,2-trifluoroacetimidate donor and a kdo acceptor has been successfully achieved for the assembly of the tetrasaccharide skeleton.201526375291
evaluating the role of phage-shock protein a in burkholderia pseudomallei.the phage-shock protein (psp) response is an extracytoplasmic response system that is vital for maintenance of the cytoplasmic membrane when the cell encounters stressful conditions. the paradigm of the psp response has been established in escherichia coli. the response has been shown to be important for survival during the stationary phase, maintenance of the proton motive force across membranes and implicated in virulence. in this study, we identified a putative pspa homologue in burkholderia ...201526374246
immune profiling of the progression of a balb/c mouse aerosol infection by burkholderia pseudomallei and the therapeutic implications of targeting hmgb1.the role of damage-associated molecular pattern hmgb1 signalling in a murine balb/c model of severe respiratory melioidosis (burkholderia pseudomallei infection) was explored in this study.201526358857
a unique set of the burkholderia collagen-like proteins provides insight into pathogenesis, genome evolution and niche adaptation, and infection detection.burkholderia pseudomallei and burkholderia mallei, classified as category b priority pathogens, are significant human and animal pathogens that are highly infectious and broad-spectrum antibiotic resistant. currently, the pathogenicity mechanisms utilized by burkholderia are not fully understood, and correct diagnosis of b. pseudomallei and b. mallei infection remains a challenge due to limited detection methods. here, we provide a comprehensive analysis of a set of 13 novel burkholderia collage ...201526356298
inactivation of burkholderia pseudomallei on environmental surfaces using spray-applied, common liquid disinfectants.five commercially available liquid antimicrobials were evaluated for their ability to decontaminate common environmental surface materials, contaminated with burkholderia pseudomallei, using a spray-based disinfectant delivery procedure. tests were conducted at both an ambient temperature (c. 20°c) and a lower temperature (c. 12°c) condition. nonporous materials (glass and aluminium) were more easily decontaminated than porous materials (wood, concrete and carpet). citric acid (1%) demonstrated ...201526331308
morphological alteration and survival of burkholderia pseudomallei in soil microcosms.the resilience of burkholderia pseudomallei, the causative agent of melioidosis, was evaluated in control soil microcosms and in soil microcosms containing nacl or feso4 at 30°c. iron (fe(ii)) promoted the growth of b. pseudomallei during the 30-day observation, contrary to the presence of 1.5% and 3% nacl. scanning electron micrographs of b. pseudomallei in soil revealed their morphological alteration from rod to coccoid and the formation of microcolonies. the smallest b. pseudomallei cells wer ...201526324731
the blood transcriptome of experimental melioidosis reflects disease severity and shows considerable similarity with the human disease.melioidosis, a severe human disease caused by the bacterium burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection. murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. in this study, mice were intranasally infected with either hi ...201526311902
cutaneous melioidosis with unusual histological features.melioidosis is caused by the saprophytic gram-negative bacillus burkholderia pseudomallei, and has varied presentations, with cutaneous manifestations occurring in about 13% of cases. the usual histopathological features of melioidosis are suppurative to chronic granulomatous inflammation. recommended treatment of melioidosis is sequential use of intravenous followed by oral antibiotics for a few months, although oral antibiotics alone can be used in primary cutaneous melioidosis. we report a ca ...201626299451
genome sequence of a burkholderia pseudomallei clinical isolate from a patient with community-acquired pneumonia and septicemia.here, we report the draft genome sequence of burkholderia pseudomallei cm_manipal, the causative agent of melioidosis isolated from a diabetic patient in manipal, southern india. the draft genome consists of 107 contigs and is 7,209,157 bp long. a total of 5,600 coding sequences (cdss), 60 trnas, 12 rrnas, and one noncoding rna (ncrna) were predicted from this assembly.201526294629
a reverse-phase protein microarray-based screen identifies host signaling dynamics upon burkholderia spp. infection.burkholderia is a diverse genus of gram-negative bacteria that causes high mortality rate in humans, equines and cattle. the lack of effective therapeutic treatments poses serious public health threats. developing insights toward host-burkholderia spp. interaction is critical for understanding the pathogenesis of infection as well as identifying therapeutic targets for drug development. reverse-phase protein microarray technology was previously proven to identify and characterize novel biomarker ...201526284031
melioidosis in hainan, china: a restrospective study.melioidosis is a tropical disease caused by infection with burkholderia pseudomallei. here, we report an 11 year (2002-2013) retrospective study of melioidosis cases in china.201526276499
neuromelioidosis: craniospinal mri findings in burkholderia pseudomallei infection.to investigate magnetic resonance imaging (mri) findings of central nervous system (cns) infection with burkholderia pseudomallei.201726256582
melioidosis and renal failure in a dutch man after a trip to gambia.melioidosis is due to burkholderia pseudomallei and is known to be endemic in south-east asia, while epidemiology of disease in sub-saharan africa is still unclear. prompt recognition of infection is crucial for adequate antibiotic treatment. infection can lead to visceral abcesses and awareness of this complication is important for proper management.201526228196
sequence- and structure-based immunoreactive epitope discovery for burkholderia pseudomallei flagellin.burkholderia pseudomallei is a gram-negative bacterium responsible for melioidosis, a serious and often fatal infectious disease that is poorly controlled by existing treatments. due to its inherent resistance to the major antibiotic classes and its facultative intracellular pathogenicity, an effective vaccine would be extremely desirable, along with appropriate prevention and therapeutic management. one of the main subunit vaccine candidates is flagellin of burkholderia pseudomallei (flicbp). h ...201526222657
melioidosis presenting as a mycotic aneurysm in a korean patient, diagnosed by 16s rrna sequencing and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.a case of melioidosis with a mycotic aneurysm is reported. the blood and tissue isolates were identified as three different species of burkholderia using the automated identification systems, vitek 2 and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms). the isolate was confirmed as burkholderia pseudomallei by 16s rrna sequencing. the typical features of the gram staining of colonies and 16s rrna sequencing can be useful to identify b. pseudomallei.201526216763
neutrophil extracellular traps in the host defense against sepsis induced by burkholderia pseudomallei (melioidosis).neutrophil extracellular traps (nets) are a central player in the host response to bacteria: neutrophils release extracellular dna (nucleosomes) and neutrophil elastase to entrap and kill bacteria. we studied the role of nets in burkholderia pseudomallei infection (melioidosis), an important cause of gram-negative sepsis in southeast asia.201426215706
burkholderia pseudomallei capsular polysaccharide recognition by a monoclonal antibody reveals key details toward a biodefense vaccine and diagnostics against melioidosis.burkholderia pseudomallei is the bacterium responsible for melioidosis, an infectious disease with high mortality rates. since melioidosis is a significant public health concern in endemic regions and the organism is currently classified as a potential biothreat agent, the development of effective vaccines and rapid diagnostics is a priority. the capsular polysaccharide (cps) expressed by b. pseudomallei is a highly conserved virulence factor and a protective antigen. because of this, cps is con ...201526198038
comparison of the early host immune response to two widely diverse virulent strains of burkholderia pseudomallei that cause acute or chronic infections in balb/c mice.burkholderia pseudomallei is the etiologic agent of melioidosis, which is endemic in southeast asia and northern australia. we previously found by the intraperitoneal (ip) route that we could discern differences in virulence in mice amongst different strains of b. pseudomallei. we report an early immune response study comparing two strains in our collection which represent the least, b. pseudomallei 1106a, and one of the most, hbpub10134a, virulent strains in balb/c mice. b. pseudomallei hbpub10 ...201526162294
bacterial reductionism: host thiols enhance virulence.intracellular bacteria exploit host cytosolic signals to upregulate virulence genes. in this issue of cell host & microbe, wong et al. (2015) show that burkholderia pseudomallei senses host cytosolic glutathione, a low-molecular-weight thiol, through the membrane-bound histidine sensor kinase vira, highlighting the importance of inter-kingdom signaling in bacterial pathogenesis.201526159714
burkholderia pseudomallei survival in lung epithelial cells benefits from mirna-mediated suppression of atg10.burkholderia pseudomallei is the causative agent of melioidosis, a disease with high mortality, which is prevalent in tropical regions of the world. a recent study shows that b. pseudomallei can survive inside mammalian cells because of its ability to actively evade cell autophagy. however, the underlying mechanisms remain unclear. in the present study, based on microarray screening, we found that atg10 was downregulated following b. pseudomallei infection in a549 human lung epithelial cells. fo ...201526151773
recombinant salmonella expressing burkholderia mallei lps o antigen provides protection in a murine model of melioidosis and glanders.burkholderia pseudomallei and burkholderia mallei are the etiologic agents of melioidosis and glanders, respectively. these bacteria are highly infectious via the respiratory route and can cause severe and often fatal diseases in humans and animals. both species are considered potential agents of biological warfare; they are classified as category b priority pathogens. currently there are no human or veterinary vaccines available against these pathogens. consequently efforts are directed towards ...201526148026
melioidosis cases and selected reports of occupational exposures to burkholderia pseudomallei--united states, 2008-2013.melioidosis is an infection caused by the gram-negative bacillus burkholderia pseudomallei, which is naturally found in water and soil in areas endemic for melioidosis. infection can be severe and sometimes fatal. the federal select agent program designates b. pseudomallei as a tier 1 overlap select agent, which can affect both humans and animals. identification of b. pseudomallei and all occupational exposures must be reported to the federal select agent program immediately (i.e., within 24 hou ...201526135734
evaluation of polysaccharide-based latex agglutination assays for the rapid detection of antibodies to burkholderia pseudomallei.melioidosis is a severe disease caused by the gram-negative bacterium burkholderia pseudomallei. diagnosis of melioidosis currently relies on the isolation of b. pseudomallei from clinical samples, which can take several days. an indirect hemagglutination assay (iha) is widely used for serodiagnosis, but it has a short shelf life, is poorly standardized, and requires a viable bacteria culture performed in a biosafety level 3 (bsl-3) laboratory. to improve the diagnostic methods, we have develope ...201526123956
identification of burkholderia pseudomallei near-neighbor species in the northern territory of australia.identification and characterization of near-neighbor species are critical to the development of robust molecular diagnostic tools for biothreat agents. one such agent, burkholderia pseudomallei, a soil bacterium and the causative agent of melioidosis, is lacking in this area because of its genomic diversity and widespread geographic distribution. the burkholderia genus contains over 60 species and occupies a large range of environments including soil, plants, rhizospheres, water, animals and hum ...201526121041
metabolomic profiling of burkholderia pseudomallei using uhplc-esi-q-tof-ms reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway.burkholderia pseudomallei is an emerging pathogen that causes melioidosis, a serious and potentially fatal disease which requires prolonged antibiotics to prevent relapse. however, diagnosis of melioidosis can be difficult, especially in culture-negative cases. while metabolomics represents an uprising tool for studying infectious diseases, there were no reports on its applications to b. pseudomallei. to search for potential specific biomarkers, we compared the metabolomics profiles of culture s ...201526097677
host cytosolic glutathione sensing by a membrane histidine kinase activates the type vi secretion system in an intracellular bacterium.type vi secretion systems (t6sss) are major virulence mechanisms in many gram-negative bacteria, but the physiological signals that activate them are not well understood. the t6ss1 of burkholderia pseudomallei is essential for pathogenesis in mammalian hosts and is only expressed when the bacterium is intracellular. we found that signals for t6ss1 activation reside in the host cytosol. through site-directed mutagenesis and biochemical studies, we identified low molecular weight thiols, particula ...201526094804
global transcriptional analysis of burkholderia pseudomallei high and low biofilm producers reveals insights into biofilm production and virulence.chronic bacterial infections occur as a result of the infecting pathogen's ability to live within a biofilm, hence escaping the detrimental effects of antibiotics and the immune defense system. burkholderia pseudomallei, a gram-negative facultative pathogen, is distinctive in its ability to survive within phagocytic and non-phagocytic cells, to persist in vivo for many years and subsequently leading to relapse as well as the development of chronic disease. the capacity to persist has been attrib ...201526092034
uncovering major genomic features of essential genes in bacteria and a methanogenic archaea.identification of essential genes is critical to understanding the physiology of a species, proposing novel drug targets and uncovering minimal gene sets required for life. although essential gene sets of several organisms have been determined using large-scale mutagenesis techniques, systematic studies addressing their conservation, genomic context and functions remain scant. here we integrate 17 essential gene sets from genome-wide in vitro screenings and three gene collections required for gr ...201526084810
[development and systematical evaluation of an up-converting phosphor technology based lateral flow assay for quantitative detection of burkholderia pseudomallei].to develop an up-converting phosphor technology-based lateral-flow (upt-lf) assay for rapid quantitative detection of burkholderia pseudomallei on site.201526081404
control of bacterial metabolism by quorum sensing.bacterial quorum sensing (qs)-dependent gene expression is a dynamic response to cell density. bacteria produce costly public goods for the benefit of the population as a whole. as an example, qs rewires cellular metabolism to produce oxalate (a public good) to enable survival during the stationary phase in burkholderia glumae, burkholderia thailandensis, and burkholderia pseudomallei. recent reports showed that qs serves as a metabolic brake to maintain homeostatic primary metabolism in b. glum ...201526072043
identification of highly pathogenic microorganisms by matrix-assisted laser desorption ionization-time of flight mass spectrometry: results of an interlaboratory ring trial.in the case of a release of highly pathogenic bacteria (hpb), there is an urgent need for rapid, accurate, and reliable diagnostics. maldi-tof mass spectrometry is a rapid, accurate, and relatively inexpensive technique that is becoming increasingly important in microbiological diagnostics to complement classical microbiology, pcr, and genotyping of hpb. in the present study, the results of a joint exercise with 11 partner institutions from nine european countries are presented. in this exercise ...201526063856
airborne transmission of melioidosis to humans from environmental aerosols contaminated with b. pseudomallei.melioidosis results from an infection with the soil-borne pathogen burkholderia pseudomallei, and cases of melioidosis usually cluster after rains or a typhoon. in an endemic area of taiwan, b. pseudomallei is primarily geographically distributed in cropped fields in the northwest of this area, whereas melioidosis cases are distributed in a densely populated district in the southeast. we hypothesized that contaminated cropped fields generated aerosols contaminated with b. pseudomallei, which wer ...201526061639
a preliminary x-ray study of 3-deoxy-d-manno-oct-2-ulosonic acid 8-phosphate phosphatase (yrbi) from burkholderia pseudomallei.3-deoxy-d-manno-oct-2-ulosonic acid 8-phosphate phosphatase (yrbi), the third enzyme in the pathway for the biosynthesis of 3-deoxy-d-manno-oct-2-ulosonic acid (kdo), hydrolyzes kdo 8-phosphate to kdo and inorganic phosphate. yrbi belongs to the haloacid dehalogenase (had) superfamily, which is a large family of magnesium-dependent phosphatase/phosphotransferase enzymes. in this study, yrbi from burkholderia pseudomallei, the causative agent of melioidosis, has been cloned, expressed, purified a ...201526057814
rapid diagnostics for melioidosis: a comparative study of a novel lateral flow antigen detection assay.the rapid diagnosis of septicaemic melioidosis will have an impact on reduction of mortality. currently, this relies almost exclusively upon culture of the causative agent burkholderia pseudomallei from clinical samples. in acute sepsis, blood is the preferred specimen for culture and therefore should be the target for a rapid diagnostic tool. a lateral flow immunoassay (lfi) for the detection of b. pseudomallei antigen has been developed. this was compared with molecular detection using the tar ...201526055557
"melioidosis in antioquia, colombia: an emerging or endemic disease? a cases series".melioidosis is endemic in malaysia, the southwest of thailand, and northern australia. the incidence in thailand is 4.4/1000000 inhabitants, where it causes 19% of community-acquired pneumonia (cap) and 20% of bacteremic pneumonia, and the mortality is 50%. sporadic cases have been described in central and south america. the objective of this study was to describe the clinical and epidemiological features and ecological characteristics of melioidosis in antioquia, colombia.201526051974
direct detection of burkholderia pseudomallei and biological factors in soil.burkholderia pseudomallei, a gram-negative saprophytic bacillus, is a severe infectious agent that causes melioidosis and soil is the most important reservoir.201526048871
burkholderia pseudomallei in soil samples from an oceanarium in hong kong detected using a sensitive pcr assay.melioidosis, caused by burkholderia pseudomallei, is an emerging infectious disease with an expanding geographical distribution. although assessment of the environmental load of b. pseudomallei is important for risk assessment in humans or animals in endemic areas, traditional methods of bacterial culture for isolation have low sensitivities and are labor-intensive. using a specific polymerase chain reaction (pcr) assay targeting a tat domain protein in comparison with a bacterial culture method ...201426038496
serum biomarkers of burkholderia mallei infection elucidated by proteomic imaging of skin and lung abscesses.the bacterium burkholderia mallei is the etiological agent of glanders, a highly contagious, often fatal zoonotic infectious disease that is also a biodefense concern. clinical laboratory assays that analyze blood or other biological fluids are the highest priority because these specimens can be collected with minimal risk to the patient. however, progress in developing sensitive assays for monitoring b. mallei infection is hampered by a shortage of useful biomarkers.201526034464
melioidosis mycotic aneurysm: an uncommon complication of an uncommon disease.melioidosis is often considered an exotic and uncommon disease in most parts of the world. however it is an endemic disease in southeast asia and northern australia with an expanding distribution. melioidosis can involve almost any organ and can deteriorate rapidly. in this report, we describe a rapidly fatal case of a mycotic aneurysm associated with melioidosis despite aggressive antibiotic therapy. the morbidity and mortality of this uncommon complication remains high despite prompt diagnosis ...201526029577
altered proteome of burkholderia pseudomallei colony variants induced by exposure to human lung epithelial cells.burkholderia pseudomallei primary diagnostic cultures demonstrate colony morphology variation associated with expression of virulence and adaptation proteins. this study aims to examine the ability of b. pseudomallei colony variants (wild type [wt] and small colony variant [scv]) to survive and replicate intracellularly in a549 cells and to identify the alterations in the protein expression of these variants, post-exposure to the a549 cells. intracellular survival and cytotoxicity assays were pe ...201525996927
macroautophagy is essential for killing of intracellular burkholderia pseudomallei in human neutrophils.neutrophils play a key role in the control of burkholderia pseudomallei, the pathogen that causes melioidosis. here, we show that survival of intracellular b. pseudomallei was significantly increased in the presence of 3-methyladenine or lysosomal cathepsin inhibitors. the lc3-flux was increased in b. pseudomallei-infected neutrophils. concordant with this result, confocal microscopy analyses using anti-lc3 antibodies revealed that b. pseudomallei-containing phagosomes partially overlapped with ...201525996656
consensus on the development of vaccines against naturally acquired melioidosis.several candidates for a vaccine against burkholderia pseudomallei, the causal bacterium of melioidosis, have been developed, and a rational approach is now needed to select and advance candidates for testing in relevant nonhuman primate models and in human clinical trials. development of such a vaccine was the topic of a meeting in the united kingdom in march 2014 attended by international candidate vaccine developers, researchers, and government health officials. the focus of the meeting was a ...201525992835
endemic melioidosis in residents of desert region after atypically intense rainfall in central australia, 2011.after heavy rains and flooding during early 2011 in the normally arid interior of australia, melioidosis was diagnosed in 6 persons over a 4-month period. although the precise global distribution of the causal bacterium burkholderia pseudomallei remains to be determined, this organism can clearly survive in harsh and even desert environments outside the wet tropics.201525988301
backbone chemical shift assignments for the sensor domain of the burkholderia pseudomallei histidine kinase riss: "missing" resonances at the dimer interface.using a deuterated sample, all the observable backbone (1)h(n), (15)n, (13)c(a), and (13)c' chemical shifts for the dimeric, periplasmic sensor domain of the burkholderia pseudomallei histidine kinase riss were assigned. approximately one-fifth of the amide resonances are "missing" in the (1)h-(15)n hsqc spectrum and map primarily onto α-helices at the dimer interface observed in a crystal structure suggesting this region either undergoes intermediate timescale motion (μs-ms) and/or is heterogen ...201525957069
melioidosis as a cause of acute abdomen in immuno-competent male from eastern india.though melioidosis is rare in india, it has gained importance as one of the most potent emerging infections. in india, the cases have been under-reported because of the lack of awareness. the majority of cases present with multifocal pyogenic infections with septicemia. we present an unusual case of melioidosis presenting as acute intestinal perforation. the organism was ceftazidime resistant, and we successfully treated the case with imipenem and doxycyclin. this case highlights ruling out the ...201725949062
case of a lung mass due to melioidosis in mexico.melioidosis, an infection caused by the gram-negative bacterium burkholderia pseudomallei, is an important cause of pneumonia, skin infection, sepsis, and death in southeast asia and australia, but is exceedingly rare in north america. pulmonary melioidosis typically presents as acute bacterial pneumonia or cavitary lung lesions resembling tuberculosis.201525943405
recent advances in burkholderia mallei and b. pseudomallei research.burkholderia mallei and burkholderia pseudomallei are gram-negative organisms, which are etiological agents of glanders and melioidosis, respectively. although only b. pseudomallei is responsible for a significant number of human cases, both organisms are classified as tier 1 select agents and their diseases lack effective diagnosis and treatment. despite a recent resurgence in research pertaining to these organisms, there are still a number of knowledge gaps. this article summarizes the latest ...201525932379
whole-genome sequence of an epidemic strain of burkholderia pseudomallei vgh07 in taiwan.here, we report the complete genome sequence of b. pseudomallei vgh07. this is an epidemic strain that was isolated from a melioidosis patient with arthro-osteomyelitis in taiwan.201525931599
complete genome sequences for 59 burkholderia isolates, both pathogenic and near neighbor.the genus burkholderia encompasses both pathogenic (including burkholderia mallei and burkholderia pseudomallei, u.s. centers for disease control and prevention category b listed), and nonpathogenic gram-negative bacilli. here we present full genome sequences for a panel of 59 burkholderia strains, selected to aid in detection assay development.201525931592
curcumin rescues caenorhabditis elegans from a burkholderia pseudomallei infection.the tropical pathogen burkholderia pseudomallei requires long-term parenteral antimicrobial treatment to eradicate the pathogen from an infected patient. however, the development of antibiotic resistance is emerging as a threat to this form of treatment. to meet the need for alternative therapeutics, we proposed a screen of natural products for compounds that do not kill the pathogen, but in turn, abrogate bacterial virulence. we suggest that the use of molecules or compounds that are non-bacter ...201525914690
effects of colonization of the roots of domestic rice (oryza sativa l. cv. amaroo) by burkholderia pseudomallei.burkholderia pseudomallei is a saprophytic bacterium that causes melioidosis and is often isolated from rice fields in southeast asia, where the infection incidence is high among rice field workers. the aim of this study was to investigate the relationship between this bacterium and rice through growth experiments where the effect of colonization of domestic rice (oryza sativa l. cv amaroo) roots by b. pseudomallei could be observed. when b. pseudomallei was exposed to surface-sterilized seeds, ...201525911477
characterization of burkholderia pseudomallei strains using a murine intraperitoneal infection model and in vitro macrophage assays.burkholderia pseudomallei, the etiologic agent of melioidosis, is a gram-negative facultative intracellular bacterium. this bacterium is endemic in southeast asia and northern australia and can infect humans and animals by several routes. it has also been estimated to present a considerable risk as a potential biothreat agent. there are currently no effective vaccines for b. pseudomallei, and antibiotic treatment can be hampered by nonspecific symptomology, the high incidence of naturally occurr ...201525909629
laboratory diagnosis of melioidosis: past, present and future.melioidosis is an emerging, potentially fatal disease caused by burkholderia pseudomallei, which requires prolonged antibiotic treatment to prevent disease relapse. however, difficulties in laboratory diagnosis of melioidosis may delay treatment and affect disease outcomes. isolation of b. pseudomallei from clinical specimens has been improved with the use of selective media. however, even with positive cultures, identification of b. pseudomallei can be difficult in clinical microbiology laborat ...201525908634
melioidosis in trinidad and tobago. 201525897877
backbone and side-chain (1)h, (15)n, (13)c assignment and secondary structure of bpsl1445 from burkholderia pseudomallei.bpsl1445 is a lipoprotein produced by the gram-negative bacterium burkholderia pseudomallei (b. pseudomallei), the etiological agent of melioidosis. immunodetection assays against sera patients using protein microarray suggest bpsl1445 involvement in melioidosis. herein we report backbone, side chain nmr assignment and secondary structure for the recombinant protein.201525893672
case-control investigation on the risk factors of melioidosis in small ruminant farms in peninsular malaysia.epidemiology of melioidosis is poorly understood because its occurrence is influenced by complex interaction of environmental, climatic, physicochemical and host factors. we investigated the potential risk factors for the exposure to burkholderia pseudomallei in small ruminants' farms in peninsular malaysia.201525891038
clear distinction between burkholderia mallei and burkholderia pseudomallei using fluorescent motb primers.a frame-shift mutation in the flagellum motor gene motb coding for the chemotaxis motb protein of burkholderia mallei has been utilized to design a conventional duplex pcr assay with fluorescent labelled primers.201525887130
whole-genome sequences of five burkholderia pseudomallei isolates from australian cystic fibrosis patients.we report here five improved high-quality draft genomes of burkholderia pseudomallei isolated from australian cystic fibrosis (cf) patients. this pathogen is rarely seen in cf patients. these genomes will be used to better understand chronic carriage of b. pseudomallei in the cf lung and the within-host evolution of longitudinal isolates from these patients.201525883282
competition between burkholderia pseudomallei and b. thailandensis.burkholderia pseudomallei is a gram-negative bacterium that causes melioidosis, an often fatal disease in tropical countries. burkholderia thailandensis is a non-virulent but closely related species. both species are soil saprophytes but are almost never isolated together.201525879538
splenic abscesses in a returning traveler.burkholderia, an aerobic gram-negative rod, is the causative organism behind melioidosis and is a common soil and water organism found predominantly in south-east asia. we report the case of a 68 year-old man returning from an extended trip to the philippines, with splenic hypodense lesions on abdominal computer tomography scan, later confirmed to be culture-positive for burkholderia pseudomallei. the patient was treated with a course of intravenous ceftazidime followed by eradication therapy wi ...201525874071
plasticity of the malleobactin pathway and its impact on siderophore action in human pathogenic bacteria.the human pathogenic bacteria burkholderia mallei, burkholderia pseudomallei, and burkholderia thailandensis harbor a highly conserved gene cluster coding for the biosynthesis of the long sought-after malleobactins. four new, unexpected congeners of the malleobactin family that were isolated and fully characterized in this study feature unusual deviations from the parent, ornibactin-like architecture. thus, the malleobactin non-ribosomal peptide synthetase (nrps) has a rare flexibility that yiel ...201525873483
burkholderia stagnalis sp. nov. and burkholderia territorii sp. nov., two novel burkholderia cepacia complex species from environmental and human sources.nine burkholderia cepacia complex (bcc) bacteria were isolated during environmental surveys for the ecological niche of burkholderia pseudomallei, the aetiological agent of melioidosis, in the northern territory of australia. they represented two multi-locus sequence analysis-based clusters, referred to as bcc b and bcc l. three additional environmental and clinical bcc b isolates were identified upon deposition of the sequences in the pubmlst database. analysis of the concatenated nucleotide se ...201525872960
intracoronary blood sampling with a microcatheter for the diagnosis of giant infective coronary aneurysm: melioidosis of coronary artery mycotic aneurysm. 201525863294
t cell immunity to the alkyl hydroperoxide reductase of burkholderia pseudomallei: a correlate of disease outcome in acute melioidosis.there is an urgent need for a better understanding of adaptive immunity to burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in southeast asia and northern australia. the imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. in several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to h ...201525862821
virulent burkholderia species mimic host actin polymerases to drive actin-based motility.burkholderia pseudomallei and b. mallei are bacterial pathogens that cause melioidosis and glanders, whereas their close relative b. thailandensis is non-pathogenic. all use the trimeric autotransporter bima to facilitate actin-based motility, host cell fusion, and dissemination. here, we show that bima orthologs mimic different host actin-polymerizing proteins. b. thailandensis bima activates the host arp2/3 complex. in contrast, b. pseudomallei and b. mallei bima mimic host ena/vasp actin poly ...201525860613
intracellular bacteria find the right motion.benanti et al. report that burkholderia pseudomallei and burkholderia mallei bacteria express proteins that mimic ena/vasp family proteins to polymerize actin, thereby inducing actin-based motility. thus, bacteria can use the various cellular actin polymerization mechanisms for intra- and inter-cellular dissemination.201525860603
exploiting molecular virulence determinants in burkholderia to develop vaccine antigens.the burkholderia genus is a highly diverse group of species that are distributed throughout a wide range of environments and habitats. among this group, which is remarkable for its adaptability to a wider range of environmental conditions including disinfectants and organic solvents, are a subgroup that represents some of the most difficult to treat infections. this subgroup includes burkholderia pseudomallei, the causative agent of melioidosis; b. mallei, the causative agent of glanders and b. ...201525850766
burkholderia pseudomallei sequencing identifies genomic clades with distinct recombination, accessory, and epigenetic profiles. 201525834186
systematic mutagenesis of genes encoding predicted autotransported proteins of burkholderia pseudomallei identifies factors mediating virulence in mice, net intracellular replication and a novel protein conferring serum resistance.burkholderia pseudomallei is the causative agent of the severe tropical disease melioidosis, which commonly presents as sepsis. the b. pseudomallei k96243 genome encodes eleven predicted autotransporters, a diverse family of secreted and outer membrane proteins often associated with virulence. in a systematic study of these autotransporters, we constructed insertion mutants in each gene predicted to encode an autotransporter and assessed them for three pathogenesis-associated phenotypes: virulen ...201525830295
evaluation of molecular methods to improve the detection of burkholderia pseudomallei in soil and water samples from laos.burkholderia pseudomallei is the cause of melioidosis, a severe and potentially fatal disease of humans and animals. it is endemic in northern australia and southeast asia and is found in soil and surface water. the environmental distribution of b. pseudomallei worldwide and within countries where it is endemic, such as the lao people's democratic republic (laos), remains unclear. however, this knowledge is important to our understanding of the ecology and epidemiology of b. pseudomallei and to ...201525819969
correction: interrogation of the burkholderia pseudomallei genome to address differential virulence among isolates.[this corrects the article doi: 10.1371/journal.pone.0115951.].201525806507
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