Publications

TitleAbstractYear(sorted descending)
Filter
PMID
Filter
melioidosis: a clinical overview.introduction melioidosis, an infection caused by the environmental gram-negative bacillus burkholderia pseudomallei, has emerged as an important cause of morbidity and mortality in southeast asia and northern australia. sources of data a review of the literature using pubmed. areas of agreement approaches to diagnosis and antimicrobial therapy. areas of controversy whether seroconversion signals the presence of a quiescent bacterial focus and an increase in long-term risk of melioidosis. areas t ...201121558159
pulmonary melioidosis in cambodia: a prospective study.abstract: background: melioidosis is a disease caused by burkholderia pseudomallei and considered endemic in south-east asia but remains poorly documented in cambodia. we report the first series of hospitalized pulmonary melioidosis cases identified in cambodia describing clinical characteristics and outcomes. methods: we characterized cases of acute lower respiratory infections (alri) that were identified through surveillance in two provincial hospitals. severity was defined by systolic blood p ...201121569563
production and characterization of chimeric monoclonal antibodies against burkholderia pseudomallei and b. mallei using the dhfr expression system.burkholderia pseudomallei (bp) and b. mallei (bm) are closely related gram-negative, facultative anaerobic bacteria which cause life-threatening melioidosis in human and glanders in horse, respectively. our laboratory has previously generated and characterized more than 100 mouse monoclonal antibodies (mabs) against bp and bm, according to in vitro and in vivo assay. in this study, 3 mabs (bp7 10b11, bp7 2c6, and bp1 7f7) were selected to develop into chimeric mouse-human monoclonal antibodies ( ...201121573027
the structure of a burkholderia pseudomallei immunophilin-inhibitor complex reveals new approaches to antimicrobial development.macrophage infectivity potentiators (mips) are a subset of immunophilins associated with virulence in a range of micro-organisms. these proteins possess prolyl-peptide isomerase activity and are inhibited by drugs including rapamycin and tacrolimus. we determined the structure of the mip homologue (bpml1) from the human pathogen and biowarfare threat burkholderia pseudomallei by nuclear magnetic resonance and x-ray crystallography. the crystal structure suggests that key catalytic residues in th ...201121574961
in vitro activity of bal30072 against burkholderia pseudomallei.burkholderia pseudomallei is an intrinsically antibiotic-resistant category b priority pathogen and the aetiological agent of melioidosis. treatment of b. pseudomallei infection is biphasic and lengthy in order to combat the acute and chronic phases of the disease. acute-phase treatment preferably involves an intravenous cephalosporin (ceftazidime) or a carbapenem (imipenem or meropenem). in this study, the anti-b. pseudomallei efficacy of a new monosulfactam, bal30072, was tested against labora ...201121596528
mucosal immunization with liposome-nucleic acid adjuvants generates effective humoral and cellular immunity.development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. we previously reported that cationic liposomes complexed with non-coding plasmid dna (cldc) were effective parenteral vaccine adjuvants. however, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. to ...201121600950
flagellar glycosylation in burkholderia pseudomallei and burkholderia thailandensis.glycosylation of proteins is known to impart novel physical properties and biological roles to proteins from both eukaryotes and prokaryotes. in this study, gel based glycoproteomics were used to identify glycoproteins of the potential bio-threat agent burkholderia pseudomallei and the closely related but non-pathogenic b. thailandensis. top-down and bottom-up ms analysis identified that the flagellin proteins of both species were post-translationally modified by novel glycans. analysis of prote ...201121602339
development and application of a cellular, gain-of-signal, bioluminescent reporter screen for inhibitors of type ii secretion in pseudomonas aeruginosa and burkholderia pseudomallei.the type ii secretion (t2s) system in gram-negative bacteria comprises the sec and tat pathways for translocating proteins into the periplasm and an outer membrane secretin for transporting proteins into the extracellular space. to discover sec/tat/t2s pathway inhibitors as potential new therapeutics, the authors used a pseudomonas aeruginosa bioluminescent reporter strain responsive to seca depletion and inhibition to screen compound libraries and characterize the hits. the reporter strain plac ...201121602485
spei restriction enzyme displays greater discriminatory power than xbai enzyme does in a pulsed-field gel electrophoresis study on 146 clinical burkholderia pseudomallei isolates.restriction enzymes spei and xbai were used in a pulsed-field gel electrophoresis (pfge) study for molecular characterization of 146 clinical burkholderia pseudomallei isolates. the pfge parameters were optimized to enable comparable, reproducible, and robust results. the optimized parameters for both spei and xbai restriction enzymes used in this study were 200 v and a pulse time of 5 to 65 s for a 28-h runtime. using spei, 9 different clusters were identified, whereas 6 clusters were identifie ...201121617308
chlorine dioxide inactivation of bacterial threat agents.aims:  to evaluate the efficacy of chlorine dioxide (clo(2) ) against seven species of bacterial threat (bt) agents in water. methods and results:  two strains of bacillus anthracis spores, yersinia pestis, francisella tularensis, burkholderia pseudomallei, burkholderia mallei, and brucella species were each inoculated into a clo(2) solution with an initial concentration of 2·0 mg l(-1) (spores only) and 0·25 mg l(-1) (all other bacteria) at ph 7 or 8, 5°c or 25°c. at 0·25 mg l(-1) in potable wa ...201121623848
the aftermath of the western australian melioidosis outbreak.abstract. melioidosis became a notifiable disease in western australia (wa) 2 years after the west kimberley melioidosis outbreak. two cases of melioidosis caused by the outbreak genotype of burkholderia pseudomallei (national collection of type cultures [nctc] 13177) occurred in 1998 and 1999 in persons who visited the outbreak location at the time. no other infections caused by the outbreak strain have been recorded in wa since that time, despite an average of four culture-positive cases per y ...201121633018
repeat blood culture positive for b. pseudomallei indicates an increased risk of death from melioidosis.abstract. melioidosis, a bacterial infection caused by burkholderia pseudomallei, is notoriously difficult to cure despite appropriate antimicrobial therapy and has a mortality rate of up to 40%. we demonstrate that a blood culture positive for b. pseudomallei taken at the end of the first and/or second week after hospitalization for melioidosis is a strong prognostic factor for death (adjusted odds ratio = 4.2, 95% confidence interval = 2.1-8.7, p < 0.001 and adjusted odds ratio = 2.6, 95% conf ...201121633019
the use of positive serological tests as evidence of exposure to burkholderia pseudomallei. 201121633045
melioidosis of the extremities in brunei darussalam.introduction: melioidosis caused by burkholderia pseudomallei is an infectious disease endemic to southeast asia and northern australia. it has a broad spectrum of clinical manifestations and high mortality, and can mimic other infectious diseases. the aim of this study was to review cases of melioidosis of the extremities in brunei darussalam. methods: culture-positive cases for burkholderia pseudomallei in raja isteri pengiran anak saleha hospital were identified from records in the microbiolo ...201121633768
rapid identification of burkholderia pseudomallei and burkholderia mallei by fluorescence in situ hybridization (fish) from culture and paraffin-embedded tissue samples.we evaluated newly developed probes for rapid identification of burkholderia (b.) pseudomallei and b. mallei and differentiation from b. thailandensis by fluorescence in situ hybridization (fish). fish correctly identified 100% of the tested b. pseudomallei (11), b. mallei (11), and b. thailandensis (1) strains, excluded 100% of all tested negative controls (61), and allowed demonstration of b. pseudomallei infection in a paraffin-embedded spleen tissue sample of an experimentally infected mouse ...201121658996
superoxide dismutase c is required for intracellular survival and virulence of burkholderia pseudomallei.burkholderia pseudomallei is an intracellular pathogen and the causative agent of melioidosis, a life-threatening disease of humans. within host cells, superoxide is an important mediator of pathogen killing. in this study, we have identified the b. pseudomallei k96243 sodc gene, shown that it has superoxide dismutase activity, and constructed an allelic deletion mutant of this gene. compared with the wild-type, the mutant was more sensitive to killing by extracellular superoxide, but not to sup ...201121659326
regulation of type vi secretion system during burkholderia pseudomallei infection.type iii and type vi secretion systems (t3sss and t6sss, respectively) are critical virulence determinants in several gram-negative pathogens. in burkholderia pseudomallei, the t3ss-3 and t6ss-1 clusters have been implicated in bacterial virulence in mammalian hosts. we recently discovered a regulatory cascade that coordinately controls the expression of t3ss-3 and t6ss-1. bsan is a central regulator located within t3ss-3 for the expression of t3ss-3 effectors and regulators for t6ss-1 such as v ...201121670170
melioidosis imported from west africa to europe.abstract. we report the first case of imported melioidosis in spain from a diabetic immigrant who visited west africa during the rainy season. because of the unusual presentation of this disease in africa, clinical and microbiological diagnosis of imported melioidosis from this continent can be very elusive.201121813848
autotransporters and their role in the virulence of burkholderia pseudomallei and burkholderia mallei.burkholderia pseudomallei and burkholderia mallei are closely related gram-negative bacteria responsible for the infectious diseases melioidosis and glanders, respectively. autotransporters (ats) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors. the b. pseudomallei k96243 genome contains 11 predicted ats, eight of which share homologs in the b. mallei atcc 23344 genome. this ...201121811486
the burkholderia pseudomallei {delta}asd mutant exhibits attenuated intracellular infectivity and imparts protection against acute inhalation melioidosis in mice.burkholderia pseudomallei, the cause of serious and life threatening diseases in humans, is of national biodefense concern because of its potential use as a bioterrorism agent. this microbe is listed as a select agent by the cdc, therefore, development of vaccines is of significant importance. here, we further investigated the growth characteristics of a recently created b. pseudomallei 1026b ?asd mutant in vitro, in a cell model, and in an animal model of infection. the mutant was typified by a ...201121807903
highly sensitive direct detection and quantification of burkholderia pseudomallei in environmental soil samples using real-time pcr.the soil bacterium and potential biothreat agent burkholderia pseudomallei causes the infectious disease melioidosis, which is naturally acquired through environmental contact with the bacterium. environmental detection of b. pseudomallei represents the basis for the development of a geographical risk map to humans and livestock. the aim of the present study was to develop a highly sensitive culture-independent dna-based method that allows direct quantification of b. pseudomallei from soil. we e ...201121803915
endovascular therapy for infected aortic aneurysms.objective: to determine the outcome of endovascular therapy for an infected aortic aneurysm in patients with or without aorto-aerodigestive/aortocaval fistulas. methods: from september 2005 to may 2010, 21 patients, 17 abdominal and four thoracic infected aortic aneurysms were treated with an endovascular stent graft at songklanagarind hospital, thailand. five patients presented with fistula complications, 1 aortoesophageal, 1 aortobronchial, 1 aortocaval, and 2 aortoenteric fistulas. lifelong a ...201121802238
neutrophils are the predominant cell-type to associate with burkholderia pseudomallei in a balb/c mouse model of respiratory melioidosis.a variety of studies have implicated neutrophils and the rapid induction of cytokine in the host response in melioidosis. here a balb/c mouse model of infection with aerosolised burkholderia pseudomalleik96243 has been used to understand the immune response to infection in this model and verify other infection models that show rapid growth of bacteria, colonisation of tissues and periphery, induction of cytokines and influx of neutrophils. uniquely, this study has also determined the association ...201121798336
combining vaccination and postexposure cpg therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis.the gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis, a major cause of lethal sepsis and morbidity in endemic areas of southeast asia and a potential bioterrorism threat. we have used susceptible balb/c mice to evaluate the potential of targeting vaccination and generic immunotherapy to the lung for optimal protection against respiratory challenge. intranasal vaccination with live attenuated b. pseudomallei increased survival and induced interferon-?-secret ...201121791666
isolation and characterization of a novel virulent podovirus which infects burkholderia pseudomallei.abstract: burkholderia pseudomallei is a saprophytic soil bacterium and the etiological agent that causes melioidosis. it is naturally resistant to many antibiotics and therefore is difficult to treat. bacteriophages may provide an alternative source of treatment. we have isolated and characterised the bacteriophage phi bp-amp1. the phage is a member of the podoviridae family and has a genome size of ~ 45 kb. molecular data based on the gene which encodes for the phage tail tubular protein sugge ...201121791081
improvement of anti-burkholderia mouse monoclonal antibody from various phage-displayed single-chain antibody libraries.to improve anti-burkholderia monoclonal antibody (mab) binding affinity, six single chain variable fragments (scfvs) constructed previously were used as scaffolds to construct large highly-diversified phage-displayed mouse scfv random and domain libraries. first, we employed random mutagenesis to introduce random point mutations into entire variable regions, generating six random libraries. additionally, the oligonucleotide-directed mutagenesis was targeted on complementarity-determining region ...201121787781
burkholderia pseudomallei-induced cell fusion in u937 macrophages can be inhibited by monoclonal antibodies against host cell surface molecules.burkholderia pseudomallei induces the formation of multinucleated giant cells in cell monolayers. after infection of human macrophage-like u937 cells with b. pseudomallei, addition of monoclonal antibodies against integrin-associated protein (cd47), e-selectin (cd62e), a fusion regulatory protein (cd98), and e-cadherin (cd324) suppressed multinucleated giant cells in a concentration-dependent manner while monoclonal antibodies against other surface molecules did not inhibit fusion despite bindin ...201121784167
antimicrobial activity of cathelicidin peptides against burkholderia pseudomallei, the causative agent of melioidosis. 201121782393
toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis.melioidosis is a tropical infection caused by the gram-negative soil saprophyte burkholderia pseudomallei. despite broad exposure of northeastern thais, disease develops in only a small proportion of individuals. although diabetes is a risk factor, the mechanisms of host susceptibility to melioidosis are still poorly understood. we postulated that toll-like receptors (tlrs) regulate host susceptibility to disease, and that genetic variation in tlrs is associated with melioidosis. we analyzed the ...201121776015
in vitro activity of sitafloxacin against burkholderia pseudomallei. 201121775108
a role for the burkholderia pseudomallei type three secretion system cluster 1 bpscn gene in virulence.burkholderia pseudomallei, the causal agent of melioidosis, employs a number of virulence factors during its infection of mammalian cells. one such factor is the type three secretion system (ttss), which is proposed to mediate the transport and secretion of bacterial effector molecules directly into host cells. the b. pseudomallei genome contains three ttss gene clusters (designated ttss1, ttss2 and ttss3). previous research has indicated that neither ttss1 nor ttss2 are involved in b. pseudomal ...201121768285
survival of burkholderia pseudomallei in distilled water for 16 years.burkholderia pseudomallei was examined after being maintained in distilled water at 25°c for 16 years. the gram stain was atypical (pale pink cocci or coccobacilli). the estimated number of live and dead b. pseudomallei was 3.8×10(7) cells/ml and 1.4×10(5) cells/ml, respectively. a colony count on agar of 1.0×10(6) cfu/ml suggested that a proportion of cells were in a viable but non-culturable state. colony morphology was different from the parental isolate for 84% of colonies. pulsed-field gel ...201121764093
etymologia: melioidosis.from the greek melis, distemper of asses, oeide-s, resemblance, and osis, a suffix indicating an abnormal condition or disease. alfred whitmore, a british pathologist serving in burma, and his assistant c. s. krishnaswami first described melioidosis in 1912. the infection became known as whitmore's disease. in 1925, ambrose t. stanton and william fletcher, the researchers who identified burkholderia pseudomallei as the infection's causative agent, renamed the infection melioidosis because of its ...201121762621
typhoon-related leptospirosis and melioidosis, taiwan, 2009.to the editor: global climatic changes have resulted in more natural disasters worldwide. these natural disasters can then cause outbreaks of emerging infectious diseases, including leptospirosis and melioidosis (1-7). in 2009, the moderate-strength typhoon morakot, with a maximum cumulative rainfall amount up to 3,059.5 mm, damaged taiwan. after this natural disaster, unusual epidemics of leptospirosis and melioidosis occurred. the main objective of this study was to clarify whether these epide ...201121762606
melioidosis in birds and burkholderia pseudomallei dispersal, australia.to the editor: melioidosis is an emerging infectious disease of humans and animals caused by the gram-negative bacterium burkholderia pseudomallei, which inhabits soil and surface water in the disease-endemic regions of southeast asia and northern australia (1). the aim of this study was to assess the potential for birds to spread b. pseudomallei. birds are known carriers of various human pathogens, including influenza viruses, west nile virus, campylobacter jejuni, and antimicrobial drug-resist ...201121762599
melioidosis acquired by traveler to nigeria.we describe melioidosis associated with travel to nigeria in a woman with diabetes, a major predisposing factor for this infection. with the prevalence of diabetes projected to increase dramatically in many developing countries, the global reach of melioidosis may expand.201121762592
melioidosis, phnom penh, cambodia.we describe 58 adult patients with melioidosis in cambodia (2007-2010). diabetes was the main risk factor (59%); 67% of infections occurred during the rainy season. bloodstream infection was present in 67% of patients, which represents 12% of all bloodstream infections. the case-fatality rate was 52% and associated with inappropriate empiric treatment.201121762590
epidemiology and investigation of melioidosis, southern arizona.burkholderia pseudomallei is a bacterium endemic to southeast asia and northern australia, but it has not been found to occur endemically in the united states. we report an ostensibly autochthonous case of melioidosis in the united states. despite an extensive investigation, the source of exposure was not identified.201121762589
burkholderia pseudomallei in unchlorinated domestic bore water, tropical northern australia.to determine whether unchlorinated bore water in northern australia contained burkholderia pseudomallei organisms, we sampled 55 bores; 18 (33%) were culture positive. multilocus sequence typing identified 15 sequence types. the b. pseudomallei sequence type from 1 water sample matched a clinical isolate from a resident with melioidosis on the same property.201121762588
burkholderia multivorans acts as an antagonist against the growth of burkholderia pseudomallei in soil.burkholderia multivorans nki379 has an antagonistic effect against the growth of b. pseudomallei, which we have demonstrated here using agar diffusion tests and a transwell system. bacterial representatives were isolated from agricultural crop soil and mixed to construct a partial bacterial community structure that based on the results of reproducible patterns following pcr-dgge (denaturing gradient gel electrophoresis) analysis from total soil chromosomes. the antagonistic effect of b. multivor ...201121752084
molecular investigations of pena-mediated ß-lactam resistance in burkholderia pseudomallei.burkholderia pseudomallei is the etiological agent of melioidosis. because of the bacterium's intrinsic resistance and propensity to establish latent infections, melioidosis therapy is complicated and prolonged. newer generation ß-lactams, specifically ceftazidime, are used for acute phase therapy, but resistance to this cephalosporin has been observed. the chromosomally encoded pena gene encodes a putative twin arginine translocase (tat)-secreted ß-lactamase, and pena mutations have been implic ...201121747814
evidence of burkholderia pseudomallei-specific immunity in patient sera persistently nonreactive by the indirect hemagglutination assay.the indirect hemagglutination assay (iha) is the most frequently used serological test to confirm exposure to burkholderia pseudomallei. patients with culture-confirmed disease often have a nonreactive iha at presentation and occasionally fail to seroconvert on serial testing. we investigated whether using antigens derived from the cultured isolates of persistently iha-nonreactive patient sera improved the sensitivity of the iha. in addition, we assessed the antigen-specific lymphocyte response ...201121677111
[a case of melioidosis occurring after a long-term stay in vietnam that developed pulmonary cavitation and relapsed with multiple pulmonary nodules].a 69-year-old man complained of fever in september 2009, after returning from vietnam where he has been working for 20 years. he had diabetes mellitus and was on diabetic oral medication. he was examined at a nearby hospital, and found out to have pneumonia with cavity formation in the right upper lobe which was found out to be not due to tuberculosis. although the patient once recovered with antibacterial medicine, after a few months, in january 2010, he was admitted to our hospital because of ...201121735746
low-dose exposure of c57bl/6 mice to burkholderia pseudomallei mimics chronic human melioidosis.burkholderia pseudomallei is the etiological agent of human melioidosis, a disease with a broad spectrum of clinical manifestations ranging from fatal septicemia to chronic localized infection or asymptomatic latent infection. most clinical and immunological studies to date have focused on the acute disease process; however, little is known about pathology and immune response in chronic melioidosis. here, we have developed a murine model of chronic disease by challenging c57bl/6 mice intranasall ...201121703409
incidence of bacteremic melioidosis in eastern and northeastern thailand.burkholderia pseudomallei, the causative agent of melioidosis, is endemic in northeastern thailand. population-based disease burden estimates are lacking and limited data on melioidosis exist from other regions of the country. using active, population-based surveillance, we measured the incidence of bacteremic melioidosis in the provinces of sa kaeo (eastern thailand) and nakhon phanom (northeastern thailand) during 2006-2008. the average annual incidence in sa kaeo and nakhon phanom per 100,000 ...201121734135
altered macrophage function is associated with severe burkholderia pseudomallei infection in a murine model of type 2 diabetes.this study used a murine model of type 2 diabetes (bks.cg-dock7(m) +/+lepr(db)/j mice) to investigate the inflammatory and cellular mechanisms predisposing to burkholderia pseudomallei infection and co-morbid diabetes. homozygous db/db (diabetic) mice developed extreme obesity, dyslipidaemia and glucose intolerance leading to hyperglycaemia and overt type 2 diabetes. compared to their heterozygous db/+ (non-diabetic) littermates, diabetic mice rapidly succumbed to subcutaneous b. pseudomallei in ...201121835260
clinical and economic burden of community-acquired pneumonia amongst adults in the asia-pacific region.community-acquired pneumonia (cap) is an important cause of mortality and morbidity amongst adults in the asia-pacific region. literature published between 1990 and may 2010 on the clinical and economic burden of cap amongst adults in this region was reviewed. cap is a significant health burden with significant economic impact in this region. chronic obstructive pulmonary disease, cardiovascular disease, diabetes mellitus and advanced age were risk factors for cap. aetiological agents included s ...201121683553
burkholderia pseudomallei: an uncommon cause of bacteraemic pneumonia in a diabetic.a 55-year-old woman presented with fever, breathlessness and shock. she was diagnosed to have diabetes mellitus (type 2) after admission. blood culture grew burkholderia pseudomallei. the patient responded to intravenous ceftozidime for two weeks and a prolonged course of six months with cotrimoxazole and doxycycline.201121838203
autophagy targeting of listeria monocytogenes and the bacterial countermeasure.autophagy acts as an intrinsic defense system against intracellular bacterial survival. recently, multiple cellular pathways that target intracellular bacterial pathogens to autophagy have been described. these include the atg5/lc3 pathway, which targets shigella, the ubiquitin (ub)-ndp52-lc3 pathway, which targets group a streptococcus (gas) and salmonella typhimurium, the ub-p62-lc3 pathway, which targets mycobacterium tuberculosis, listeria monocytogenes and s. typhimurium, and the diacylglyc ...201121193840
burkholderia pseudomallei antibodies in individuals living in endemic regions in northeastern brazil.a seroepidemiological investigation was conducted among the population of two municipalities in northeastern brazil. immunoglobulin m (igm) and igg antibodies to burkholderia pseudomallei were positive in 51.27% (161 in 317 samples) and 58.49% (186), respectively. igm titers were higher in children than in adults. on the contrary, igg increased progressively with age. we observed a significant association between agricultural occupation and raised igm titers (p < 0.005) and igg titers (p < 0.001 ...201121292903
glyburide is anti-inflammatory and associated with reduced mortality in melioidosis.patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. this k(atp)-channel blocker and broad-spectrum atp-binding cassette (abc) transporter inhibitor has broad-ranging effects on the immune system, including inhibition of inflammasome assembly and would be predicted to influence the host response to infect ...201121293047
[a case of melioidosis in argentina].we describe a case of 17-year- old man native of dominican republic, with hodgkin's lymphoma, who presented soft espontaneous draining nodules. in the clinical samples grew burkholderia pseudomallei; the etiological agent of melioidosis. he received antimicrobial treatment with imipenem and amoxicillin/clavulanic with very good clinical evolution of the infectious process. melioidosis diagnosis could be underestimated due to the low incidence of burkholderia pseudomallei in our continent. the de ...201121296719
identification of motifs of burkholderia pseudomallei bima required for intracellular motility, actin binding, and actin polymerization.actin-based motility of the melioidosis pathogen burkholderia pseudomallei requires bima (burkholderia intracellular motility a). the mechanism by which bima mediates actin assembly at the bacterial pole is ill-defined. toward an understanding of the regions of b. pseudomallei bima required for intracellular motility and the binding and polymerization of actin, we constructed plasmid-borne bima variants and glutathione-s-transferase fusion proteins with in-frame deletions of specific motifs. a 1 ...201121335455
elucidation of the regulon and cis-acting regulatory element of hrpb, the arac-type regulator of a plant pathogen-like type iii secretion system in burkholderia pseudomallei.the human pathogen burkholderia pseudomallei possesses multiple type iii secretion system (t3ss) gene clusters. one of these, the b. pseudomallei t3ss2 (t3ss2(bp)) gene cluster, which apparently plays no role in animal virulence, is also found in six additional burkholderia spp. and is very similar to t3sss found in phytopathogenic xanthomonas spp. and ralstonia solanacearum. the t3ss2(bp) gene cluster also encodes an arac-type regulatory protein (hrpb(bp)) that is an ortholog of hrpb, the maste ...201121335458
leveraging structure determination with fragment screening for infectious disease drug targets: mecp synthase from burkholderia pseudomallei.as part of the seattle structural genomics center for infectious disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. we have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. in this study, we report fragment screening methods and structure determination results for 2c-methyl-d ...201121359640
predicting the success of fragment screening by x-ray crystallography.fragment screening using x-ray crystallography is a method that can provide direct three-dimensional readouts of the structures of protein-small molecule complexes for lead development and fragment-based drug discovery. with current technology, an amenable crystal form can be screened crystallographically against a library of 1000-2000 fragments in 1-2 weeks. we have performed over a dozen crystallographic screening campaigns using our own compound collection called fragments of life™ (fol). whi ...201121371588
systemic melioidiosis. 201121378433
outer membrane proteome of burkholderia pseudomallei and burkholderia mallei from diverse growth conditions.burkholderia mallei and burkholderia pseudomallei are closely related, aerosol-infective human pathogens that cause life-threatening diseases. biochemical analyses requiring large-scale growth and manipulation at biosafety level 3 under select agent regulations are cumbersome and hazardous. we developed a simple, safe, and rapid method to prepare highly purified outer membrane (om) fragments from these pathogens. shotgun proteomic analyses of oms by trypsin shaving and mass spectrometry identifi ...201121391724
mechanism and inhibition of the fabi enoyl-acp reductase from burkholderia pseudomallei.as an initial step in developing novel antibacterials against burkholderia pseudomallei, we have characterized the fabi enoyl-acp reductase homologues in the type ii fatty acid biosynthesis pathway from this organism and performed an initial enzyme inhibition study.201121393229
bioluminescent diagnostic imaging to characterize altered respiratory tract colonization by the burkholderia pseudomallei capsule mutant.pneumonia is a common manifestation of the potentially fatal disease melioidosis, caused by the select agent bacteria burkholderia pseudomallei. in this study we describe a new model system to investigate pulmonary melioidosis in vivo using bioluminescent-engineered bacteria in a murine respiratory disease model. studies were performed to validate that the stable, light producing b. pseudomallei strain jw280 constitutively produced light in biologically relevant host-pathogen interactions. hairl ...201121720539
knockout and pullout recombineering for naturally transformable burkholderia thailandensis and burkholderia pseudomallei.phage ++-red proteins are powerful tools for pulling and knocking out chromosomal fragments but have been limited to the +¦-proteobacteria. procedures are described here to easily knock out (ko) and pull out (po) chromosomal dna fragments from naturally transformable burkholderia thailandensis and burkholderia pseudomallei. this system takes advantage of published compliant counterselectable and selectable markers (sacb, phes, gat and the arabinose-utilization operon) and ++-red mutant proteins. ...201121738123
molecular characterization of clinical burkholderia pseudomallei isolates from india.multilocus sequence typing of seven isolates of burkholderia pseudomallei from india showed considerable diversity, with six different sequence types. possible dissemination of melioidosis by historical trading routes is supported by links to strains from southeast asia, china, and africa and the presence of the burkholderia mallei allele of the bima gene.201121734136
dissection of the burkholderia intracellular life cycle using a photothermal nanoblade.burkholderia pseudomallei and burkholderia thailandensis are related pathogens that invade a variety of cell types, replicate in the cytoplasm, and spread to nearby cells. we have investigated temporal and spatial requirements for virulence determinants in the intracellular life cycle, using genetic dissection and photothermal nanoblade delivery, which allows efficient placement of bacterium-sized cargo into the cytoplasm of mammalian cells. the conserved bsa type iii secretion system (t3ss(bsa) ...201121730143
[melioidosis: a poorly known tropical disease].a 35 year-old man was admitted to the hospital for fever upon returning from the caribbean area. he died 48 hours later, after developing pulmonary lesions that were complicated by multi-organ failure, despite rapid diagnosis of melioidosis by mass spectrometry on blood cultures. melioidosis is a rare bacterial disease in the traveller that is caused by burkholderia pseudomallei. although the clinical presentation is variable, pneumonia is the most frequent finding. diagnosis may be considered i ...201121692313
alanine racemase mutants of burkholderia pseudomallei and burkholderia mallei and use of alanine racemase as a non-antibiotic-based selectable marker.burkholderia pseudomallei and burkholderia mallei are category b select agents and must be studied under bsl3 containment in the united states. they are typically resistant to multiple antibiotics, and the antibiotics used to treat b. pseudomallei or b. mallei infections may not be used as selective agents with the corresponding burkholderia species. here, we investigated alanine racemase deficient mutants of b. pseudomallei and b. mallei for development of non-antibiotic-based genetic selection ...201121720554
burkholderia pseudomallei infection in a child with cystic fibrosis: acquisition in the western hemisphere.melioidosis, an infection caused by the bacterium burkholderia pseudomallei, is endemic to southeast asia and northern australia but is only very rarely seen in patients in the united states. we report pulmonary b pseudomallei infection in a young girl with cystic fibrosis (cf) who had never traveled to asia or australia. biochemical and epidemiologic investigation determined aruba as the likely site of disease acquisition. this report highlights the ability of patients with cf to acquire this o ...201121729895
acute melioid community-acquired pneumonia.to better understand the characteristics of patients with acute melioid community-acquired pneumonia (cap) on emergency department (ed) arrival, and the risk factors in patients with acute melioid cap that differ from those in patients with severe cap of causes other than melioidosis.201121696989
a novel fk-506-binding-like protein that lacks peptidyl-prolyl isomerase activity is involved in intracellular infection and in vivo virulence of burkholderia pseudomallei.burkholderia pseudomallei is a facultative intracellular bacterial pathogen causing melioidosis, an often fatal infectious disease that is endemic in several tropical and subtropical areas around the world. we previously described a ptk2 cell-based plaque assay screening system of b. pseudomallei transposon mutants that led to the identification of several novel virulence determinants. using this approach we identified a mutant with reduced plaque formation in which the bpsl0918 gene was disrupt ...201121680634
a naturally derived outer-membrane vesicle vaccine protects against lethal pulmonary burkholderia pseudomallei infection.burkholderia pseudomallei, and other members of the burkholderia, are among the most antibiotic-resistant bacterial species encountered in human infection. mortality rates associated with severe b. pseudomallei infection approach 50% despite therapeutic treatment. a protective vaccine against b. pseudomallei would dramatically reduce morbidity and mortality in endemic areas and provide a safeguard for the u.s. and other countries against biological attack with this organism. in this study, we in ...201121871517
A Burkholderia pseudomallei toxin inhibits helicase activity of translation factor eIF4A.The structure of BPSL1549, a protein of unknown function from Burkholderia pseudomallei, reveals a similarity to Escherichia coli cytotoxic necrotizing factor 1. We found that BPSL1549 acted as a potent cytotoxin against eukaryotic cells and was lethal when administered to mice. Expression levels of bpsl1549 correlate with conditions expected to promote or suppress pathogenicity. BPSL1549 promotes deamidation of glutamine-339 of the translation initiation factor eIF4A, abolishing its helicase ac ...201122076380
a proteome reference map of the causative agent of melioidosis burkholderia pseudomallei.burkholderia pseudomallei is the etiologic agent of melioidosis. using 2de and maldi-tof ms, we report here a proteome reference map constructed from early stationary phase, a bacterial adaptation process. we identified 282 protein spots representing 220 orfs; many of them have been implicated in bacterial pathogenesis. up to 20% of identified orfs belong to post-translational modification and stress responses. the proteome reference map will support future analysis of the bacterial gene and env ...201121960737
Antimicrobial resistance to ceftazidime involving loss of penicillin-binding protein 3 in Burkholderia pseudomallei.Known mechanisms of resistance to ß-lactam antibiotics include ß-lactamase expression, altered drug target, decreased bacterial permeability, and increased drug efflux. Here, we describe a unique mechanism of ß-lactam resistance in the biothreat organism Burkholderia pseudomallei (the cause of melioidosis), associated with treatment failure during prolonged ceftazidime therapy of natural infection. Detailed comparisons of the initial ceftazidime-susceptible infecting isolate and subsequent cefta ...201121969582
Two Norwegian patients with melioidosis presenting with bacteraemia and splenic and prostatic abscesses.Infections caused by Burkholderia pseudomallei are rare in nonendemic areas, such as Scandinavia. We report the first two cases of melioidosis in Norway presenting with bacteraemia and splenic and prostatic abscesses, respectively.201122017720
Structural basis of the substrate specificity of bifunctional isocitrate dehydrogenase kinase/phosphatase.Isocitrate dehydrogenase kinase/phosphatase (AceK) regulates entry into the glyoxylate bypass by reversibly phosphorylating isocitrate dehydrogenase (ICDH). On the basis of the recently determined structure of the AceK-ICDH complex from Escherichia coli, we have classified the structures of homodimeric NADP(+)-ICDHs to rationalize and predict which organisms likely contain substrates for AceK. One example is Burkholderia pseudomallei (Bp). Here we report a crystal structure of Bp-ICDH that exhib ...201121870819
A Burkholderia pseudomallei macrophage infectivity potentiator-like protein has rapamycin-inhibitable peptidylprolyl isomerase activity and pleiotropic effects on virulence.Macrophage infectivity potentiators (Mips) are a group of virulence factors encoded by pathogenic bacteria such as Legionella, Chlamydia, and Neisseria species. Mips are part of the FK506-binding protein (FKBP) family, whose members typically exhibit peptidylprolyl cis-trans isomerase (PPIase) activity which is inhibitable by the immunosuppressants FK506 and rapamycin. Here we describe the identification and characterization of BPSS1823, a Mip-like protein in the intracellular pathogen Burkholde ...201121859853
[Detection and identification of highly pathogenic bacteria within the framework of the EQADeBa project--Part I: Samples containing living pathogens].Bacillus anthracis, Yersinia pestis, Francisella tularensis, Brucella sp., Bulkholderia mallei are B. pseudomallei are highly pathogenic bacteria of potential bioterrorism risk. To support the early warning and rapid response capacity to ensure an effective reaction to bioterrorist attacks the international project "Establishment of Quality Assurances for Detection of Highly Pathogenic Bacteria of Potential Bioterrorism Risk" (EQADeBa) has been established. The aim of the project was establishme ...201122184939
bopc is a type iii secreted effector protein of burkholderia pseudomallei.burkholderia pseudomallei, the causative agent of melioidosis, exploits the bsa type iii secretion system (t3ss) to deliver effector proteins into host cells. these effectors manipulate host cell functions; thus, contributing to the ability of the bacteria to evade the immune response and cause disease. only two bsa-secreted effectors have been conclusively identified to date. here, we report the identification of the third b. pseudomallei type iii secreted effector protein, designated bopc. bop ...201122092682
identification of circulating bacterial antigens by in vivo microbial antigen discovery.detection of microbial antigens in clinical samples can lead to rapid diagnosis of an infection and administration of appropriate therapeutics. a major barrier in diagnostics development is determining which of the potentially hundreds or thousands of antigens produced by a microbe are actually present in patient samples in detectable amounts against a background of innumerable host proteins. in this report, we describe a strategy, termed in vivo microbial antigen discovery (inmad), that we used ...201121846829
immunogenic consensus sequence t helper epitopes for a pan-burkholderia biodefense vaccine.biodefense vaccines against category b bioterror agents burkholderia pseudomallei (bpm) and burkholderia mallei (bm) are needed, as they are both easily accessible to terrorists and have strong weaponization potential. burkholderia cepaciae (bc), a related pathogen, causes chronic lung infections in cystic fibrosis patients. since bpm, bm and bc are all intracellular bacteria, they are excellent targets for t cell-based vaccines. however, the sheer volume of available genomic data requires the a ...201125346775
perasafe, virkon and bleach are bactericidal for burkholderia pseudomallei, a select agent and the cause of melioidosis. 201120832143
a conference report from "down under": talking autophagy at ozbio2010.ozbio2010 was held at the melbourne convention and exhibition centre, september 26 to october 1, 2010. this international conference catered to researchers in several fields having complementary interests including biochemistry, molecular biology, cell biology, plant physiology and health-related research. it was held under the auspices of two major international scientific societies, iubmb and faobmb, and the combio2010 collective (representing nine professional societies and groupings from aus ...201121116128
impact of streptozotocin-induced diabetes on functional responses of dendritic cells and macrophages towards burkholderia pseudomallei.diabetes mellitus is a documented risk factor for melioidosis, a tropical infection caused by burkholderia pseudomallei. the increased susceptibility of diabetic individuals to infections with other pathogens has been associated with immune dysregulation. however, the impact of diabetes on the functional responses of dendritic cells (dc) and macrophages during b. pseudomallei infection has not been investigated. this study compared the responses of macrophages and dc towards b. pseudomallei usin ...201121204999
fatal acute melioidosis in a tourist returning from martinique island, november 2010.we report the fatal case of acute melioidosis in a patient returning from martinique with fever in november 2010. gram-negative rods were isolated from a blood culture and burkholderia pseudomallei identified within 24 hours after first medical contact. the patient died two days after admission to hospital despite intravenous therapy with high doses of imipenem/cilastatin and intensive care. clinicians seeing travellers returning from the subtropics or tropics with severe pneumonia or septicaemi ...201121223835
macrophage and galleria mellonella infection models reflect the virulence of naturally occurring isolates of b. pseudomallei, b. thailandensis and b. oklahomensis.burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. in murine models of infection, different strains exhibit varying degrees of virulence. in contrast, two related species, b. thailandensis and b. oklahomensis, are highly attenuated in mice. our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (galleria mellonella) infection models.201121241461
burkavidin: a novel secreted biotin-binding protein from the human pathogen burkholderia pseudomallei.the avidin-biotin technology has many applications, including molecular detection; immobilization; protein purification; construction of supramolecular assemblies and artificial metalloenzymes. here we present the recombinant expression of novel biotin-binding proteins from bacteria and the purification and characterization of a secreted burkavidin from the human pathogen burkholderia pseudomallei. expression of the native burkavidin in escherichia coli led to periplasmic secretion and formation ...201121241807
metabolites from the induced expression of cryptic single operons found in the genome of burkholderia pseudomallei.bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. a subset of these cryptic genetic elements appears as individual operons. here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium burkholderia pseudomallei . placing these operons under the control of an inducible promoter led to the production of seven new metabolites. among the molecules w ...201121247113
n-octanoylhomoserine lactone signalling mediated by the bpsi-bpsr quorum sensing system plays a major role in biofilm formation of burkholderia pseudomallei.the genome of burkholderia pseudomallei encodes three acylhomoserine lactone (ahl) quorum sensing systems, each comprising an ahl synthase and a signal receptor/regulator. the bpsi-bpsr system produces n-octanoylhomoserine lactone (c8hl) and is positively auto-regulated by its ahl product. the products of the remaining two systems have not been identified. in this study, tandem ms was used to identify and quantify the ahl species produced by three clinical b. pseudomallei isolates - khw, k96243 ...201121252275
reduced susceptibility of malaysian clinical isolates of burkholderia pseudomallei to ciprofloxacin.ciprofloxacin, a quinolone with good intracellular penetration may possibly be used for treatment of melioidosis caused by burkholderia pseudomallei, but problems with resistance may be encountered. amino acid substitutions in gyra/gyrb have given rise to fluoroquinolone resistance in various microorganisms. using published primers for gyra and gyrb, pcr was performed on 11 isolates of b. pseudomallei with varying degrees of sensitivity to ciprofloxacin, followed by dna sequencing to detect poss ...201122433895
surface plasmon resonance immunosensor for rapid and specific diagnosis of melioidosis antibody.melioidosis, caused by burkholderia pseudomallei, is a potentially fatal disease, which requires an accurate and rapid diagnosis. this paper reports on the highly sensitive and specific detection of melioidosis antibodies by surface plasmon resonance immunosensor. the sensing surface was immobilized with b. pseudomallei bipd protein via a 11-mercaptoundecanoic acid self-assembled monolayer. under optimum conditions individual sera of melioidosis patients, non-melioidosis patients (negative) and ...201122299443
immune response to burkholderia pseudomallei.burkholderia pseudomallei are the causative agents of melioidosis, a disease found mostly in people with underlying risk factors. fifty percent of cases are community-acquired septicemias and manifestation can vary from acute septicemia (with or without shock), to chronic, to subclinical infections. there is no vaccine to prevent the condition. it is difficult to eradicate the bacteria. prolonged antibiotic therapy is required. finally, there is a high rate of relapse when therapy is not complet ...201122256484
the bug and the big heart --melioidotic pericardial effusion.melioidosis is an infection caused by gram negative bacterium burkholderia pseudomallei leading to abscesses in lungs, liver, spleen, musculoskeletal system, prostate and sepsis. we present a rare case of purulent pericardial effusion caused by melioidosis with concomitant pneumonia and splenic abscesses. the patient underwent pericardiocentesis and successfully recovered from cardiogenic and septic shock.201123765151
melioidosis: it is not far from here.in the modern world, with developed traveling facilities, tourism is an important factor in emerging new infectious diseases in non-endemic areas. therefore, the epidemiology of infections is a considerable issue for physicians and should be taken into account. we report a case of melioidosis in a 69-year-old iranian man during his trip to southeast asia. on admission, he was febrile with tachycardia and tachypnea and had diabetes mellitus and hypertension since eleven years ago. bronchoscopy an ...201125191391
identification of immunoreactive secretory proteins from the stationary phase culture of burkholderia pseudomallei.bacterial secreted proteins are known to be involved in virulence and may mediate important host-pathogen interactions. in this study, when the stationary phase culture supernatant of burkholderia pseudomallei was subjected to 2-de, 113 protein spots were detected. fifty-four of the secreted proteins, which included metabolic enzymes, transcription/translation regulators, potential virulence factors, chaperones, transport regulators, and hypothetical proteins, were identified using ms and databa ...201021254130
development of ceftazidime resistance in burkhoderia pseudomallei in a patient experiencing melioidosis with mediastinal lymphadenitis. 201021274496
the epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year darwin prospective study.over 20 years, from october 1989, the darwin prospective melioidosis study has documented 540 cases from tropical australia, providing new insights into epidemiology and the clinical spectrum.201021152057
identification of immunoreactive secretory proteins from the stationary phase culture of burkholderia pseudomallei.bacterial secreted proteins are known to be involved in virulence and may mediate important host-pathogen interactions. in this study, when the stationary phase culture supernatant of burkholderia pseudomallei was subjected to 2-de, 113 protein spots were detected. fifty-four of the secreted proteins, which included metabolic enzymes, transcription/translation regulators, potential virulence factors, chaperones, transport regulators, and hypothetical proteins, were identified using ms and databa ...201021170972
construction and molecular characterization of mouse single-chain variable fragment antibodies against burkholderia mallei and burkholderia pseudomallei.we have selected two lipopolysaccharide (lps) specific burkholderia mallei mouse monoclonal antibodies (mabs) and four anti-capsular b. pseudomallei-specific mabs to generate mouse single-chain variable fragment (scfv) antibodies. this selection was made through extensive in vitro and in vivo assay from our library of mabs against b. mallei and b. pseudomallei. we initially generated the mouse immunoglobulin variable heavy chain (vh) and light chain (vl) regions from each of these six selected m ...201021172353
novel pan-genomic analysis approach in target selection for multiplex pcr identification and detection of burkholderia pseudomallei, burkholderia thailandensis, and burkholderia cepacia complex species: a proof-of-concept study.burkholderia pseudomallei, burkholderia thailandensis, and the burkholderia cepacia complex differ greatly in pathogenicity and epidemiology. yet, they are occasionally misidentified by biochemical profiling, and even 16s rrna gene sequencing may not offer adequate discrimination between certain species groups. using the 23 b. pseudomallei, four b. thailandensis, and 16 b. cepacia complex genome sequences available, we identified gene targets specific to each of them (a tat domain protein, a 70- ...201021177905
immunospecific responses to bacterial elongation factor tu during burkholderia infection and immunization.burkholderia pseudomallei is the etiological agent of melioidosis, a disease endemic in parts of southeast asia and northern australia. currently there is no licensed vaccine against infection with this biological threat agent. in this study, we employed an immunoproteomic approach and identified bacterial elongation factor-tu (ef-tu) as a potential vaccine antigen. ef-tu is membrane-associated, secreted in outer membrane vesicles (omvs), and immunogenic during burkholderia infection in the muri ...201021179405
cd4+ t-cell immunity to the burkholderia pseudomallei abc transporter lolc in melioidosis.burkholderia pseudomallei causes melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. this spectrum of host-pathogen interactions poses challenging questions about the heterogeneity in immunity to b. pseudomallei. models show protection to be dependent on cd4(+) cells and ifn-γ, but little is known about specific target antigens. having previously implicated the abc transporter, lolc, in protective immunity, we here use epitope pred ...201021182082
Refresh
firstprev
12345678910...
nextlast
Displaying items 901 - 1000 of 2531