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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
structural analysis of capsular polysaccharides expressed by burkholderia mallei and burkholderia pseudomallei.capsular polysaccharides (cpss) were isolated from o-polysaccharide deficient strains of burkholderia mallei and burkholderia pseudomallei using a modified hot phenol/water extraction procedure. glycosyl composition, methylation, maldi-tof ms analyses as well as (1)h nmr spectroscopy including cosy, tocsy, noesy, hmbc and hsqc experiments identified the presence of two distinct cps antigens in the samples exhibiting the following structures: this study confirms the ability of b. mallei to expres ...201122221792
development of multiplex real-time pcr for the rapid detection of five bacterial causes of community acquired pneumonia.establishing a microbial diagnosis for patients with community-acquired pneumonia (cap) is still challenging and is often achieved in only 30-50% of cases. polymerase chain reaction (pcr) has been shown to be more sensitive than conventional microbiological methods and it could help to increase the microbial yield for cap patients. this study was designed to develop, optimize and evaluate multiplex real-time pcr as a method for rapid differential detection of five bacterial causes of cap namely ...201122433883
the use of multiplex real-time pcr improves the detection of the bacterial etiology of community acquired pneumonia.community-acquired pneumonia (cap) is still a major cause of morbidity and mortality especially to children and compromised hosts, such as the old and those with underlying chronic diseases. knowledge of pathogens causing cap constitutes the basis for selection of antimicrobial treatment. previous data have shown that etiological agents can be identified in only up to 50% of patients, but this figure can be improved by using polymerase chain reaction (pcr). this study was designed to evaluate mu ...201122433882
heterologously type iv pilus expressed protein of burkholderia pseudomallei is immunogenic but fails to induce protective immunity in mice.burkholderia pseudomallei is the causative agent of melioidosis, a severe disease of humans and animals. at present, no effective vaccine against melioidosis exists. bacterial type iv pilin proteins have been used successfully as subunit vaccines. in this study, we evaluated a heterologously expressed and purified type iv pilus protein (pilv) of b. pseudomallei strain k96243 as a candidate subunit vaccine. pilv protein was assessed for its ability to protect balb/c mice against b. pseudomallei s ...201122299445
defense mechanisms of hepatocytes against burkholderia pseudomallei.the gram-negative facultative intracellular rod burkholderia pseudomallei causes melioidosis, an infectious disease with a wide range of clinical presentations. among the observed visceral abscesses, the liver is commonly affected. however, neither this organotropism of b. pseudomallei nor local hepatic defense mechanisms have been thoroughly investigated so far. own previous studies using electron microscopy of the murine liver after systemic infection of mice indicated that hepatocytes might b ...201122291688
inflammasome-dependent pyroptosis and il-18 protect against burkholderia pseudomallei lung infection while il-1β is deleterious.burkholderia pseudomallei is a gram-negative bacterium that infects macrophages and other cell types and causes melioidosis. the interaction of b. pseudomallei with the inflammasome and the role of pyroptosis, il-1β, and il-18 during melioidosis have not been investigated in detail. here we show that the nod-like receptors (nlr) nlrp3 and nlrc4 differentially regulate pyroptosis and production of il-1β and il-18 and are critical for inflammasome-mediated resistance to melioidosis. in vitro produ ...201122241982
infectious diseases of khmer immigrants in the united states: review of published reports.infectious diseases are influenced by where patients have lived or travelled in the past, e.g., infection with schistosoma mekongi can be acquired during freshwater contact in cambodia, but not in the united states. here the infectious diseases of khmer immigrants in the united states were studied by reviewing published reports. thirteen case series and 9 case reports of 5,222 patients were identified. most reports were of infections with gastrointestinal parasites (8, 36%), plasmnodium species ...201123272458
diagnostic use of burkholderia pseudomallei selective media in a low prevalence setting.routine use of selective media improves diagnosis of burkholderia pseudomallei, but resources may be limited in endemic developing countries. to maximise yield in the relatively low-prevalence setting of kuala lumpur, malaysia, b. pseudomallei selective agar and broth were compared with routine media for 154 respiratory specimens from patients with community-acquired disease. selective media detected three additional culture-positive specimens and one additional melioidosis patient, at a consuma ...201122112687
Musculoskeletal melioidosis.Melioidosis is an infectious disease caused by Burkholderia pseudomallei, mostly affecting patients in Southeast Asia and northern Australia. The disease has been increasingly recognized around the world due to the increased levels of travel and population movement. Clinical manifestations of melioidosis range from fulminant septicemic illness to an indolent local infection. The disease often involves multiple organs, including the lung, spleen, liver, and other visceral organs. Musculoskeletal ...201122081283
cloning, purification and crystallographic analysis of a hypothetical protein, bpsl1549, from burkholderia pseudomallei.burkholderia pseudomallei bpsl1549, a putative protein of unknown function, has been overexpressed in escherichia coli, purified and subsequently crystallized by the hanging-drop vapour-diffusion method using peg as a precipitant to give crystals with overall dimensions of 0.15 × 0.15 × 0.1 mm. native data were collected to 1.47 å resolution at the european synchrotron radiation facility (esrf). the crystals belonged to space group p2(1)2(1)2(1), with unit-cell parameters a = 37.1, b = 45.4, c = ...201122139182
structures of phosphopantetheine adenylyltransferase from burkholderia pseudomallei.phosphopantetheine adenylyltransferase (ppat) catalyzes the fourth of five steps in the coenzyme a biosynthetic pathway, reversibly transferring an adenylyl group from atp onto 4'-phosphopantetheine to yield dephospho-coenzyme a and pyrophosphate. burkholderia pseudomallei is a soil- and water-borne pathogenic bacterium and the etiologic agent of melioidosis, a potentially fatal systemic disease present in southeast asia. two crystal structures are presented of the ppat from b. pseudomallei with ...201121904046
Groundwater seeps facilitate exposure to Burkholderia pseudomallei.Burkholderia pseudomallei is a saprophytic bacterium which is the causative agent of melioidosis, a common cause of fatal bacterial pneumonia and sepsis in the tropics. The incidence of melioidosis is clustered spatially and temporally and is heavily linked to rainfall and extreme weather events. Clinical case clustering has recently been reported in Townsville, Australia, and has implicated Castle Hill, a granite monolith in the city center, as a potential reservoir of infection. Topsoil and wa ...201121873480
Molecular investigations of a locally acquired case of melioidosis in Southern AZ, USA.Melioidosis is caused by Burkholderia pseudomallei, a Gram-negative bacillus, primarily found in soils in Southeast Asia and northern Australia. A recent case of melioidosis in non-endemic Arizona was determined to be the result of locally acquired infection, as the patient had no travel history to endemic regions and no previous history of disease. Diagnosis of the case was confirmed through multiple microbiologic and molecular techniques. To enhance the epidemiological analysis, we conducted s ...201122028940
Survey of antimicrobial resistance in clinical Burkholderia pseudomallei isolates over two decades in Northeast Thailand.A 21-year survey conducted in northeast Thailand of antimicrobial resistance to parenteral antimicrobial drugs used to treat melioidosis identified 24/4,021 (0.6%) patients with one or more isolates resistant to ceftazidime (n = 8), amoxicillin-clavulanic acid (n = 4), or both drugs (n = 12). Two cases were identified at admission, and the remainder were detected a median of 15 days after starting antimicrobial therapy. Resistance to carbapenem drugs was not detected. These findings support the ...201121876049
Development of vaccines against burkholderia pseudomallei.Burkholderia pseudomallei is a Gram-negative bacterium which is the causative agent of melioidosis, a disease which carries a high mortality and morbidity rate in endemic areas of South East Asia and Northern Australia. At present there is no available human vaccine that protects against B. pseudomallei, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. This review considers the multiple elements of melioidosis ...201121991263
diabetes does not influence activation of coagulation, fibrinolysis or anticoagulant pathways in gram-negative sepsis (melioidosis).diabetes is associated with a disturbance of the haemostatic balance and is an important risk factor for sepsis, but the influence of diabetes on the pathogenesis of sepsis remains unclear. melioidosis ( burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in southeast asia and northern australia. we sought to investigate the impact of pre-existing diabetes on the coagulation and fibrinolytic systems during sepsis caused by b.pseudomallei . we recruited a cohort of ...201121979378
facile syntheses of the disaccharide repeating unit of the o-antigenic polysaccharide of burkholderia pseudomallei strain 304b and its dimer and trimer.a highly efficient strategy for the preparation of a disaccharide-repeating unit of the o-antigenic polysaccharide of burkholderia pseudomallei strain 304b, and its dimer and trimer, has been developed through a regio- and stereoselective manner using p-methoxylphenyl 2,4,6-tri-o-benzoyl-α-d-glucopyranoside and 3-o-allyloxycarbonyl-2,4-di-o-benzoyl-6-deoxy-α-l-talopyranosyl trichloroacetimidate as the key synthons. the target molecules were equipped with a p-methoxylphenyl handle at the reducing ...201121963340
epidemiological tracking and population assignment of the non-clonal bacterium, burkholderia pseudomallei.rapid assignment of bacterial pathogens into predefined populations is an important first step for epidemiological tracking. for clonal species, a single allele can theoretically define a population. for non-clonal species such as burkholderia pseudomallei, however, shared allelic states between distantly related isolates make it more difficult to identify population defining characteristics. two distinct b. pseudomallei populations have been previously identified using multilocus sequence typin ...201122180792
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
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
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
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
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
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
renal allograft recipient with melioidosis of the urinary tract. 201121299774
human immune responses to burkholderia pseudomallei characterized by protein microarray analysis.we aimed to determine the antibody and t cell responses to burkholderia pseudomallei of humans to select candidate vaccine antigens.201121300673
the cluster 1 type vi secretion system is a major virulence determinant in burkholderia pseudomallei.the burkholderia pseudomallei k96243 genome encodes six type vi secretion systems (t6sss), but little is known about the role of these systems in the biology of b. pseudomallei. in this study, we purified recombinant hcp proteins from each t6ss and tested them as vaccine candidates in the balb/c mouse model of melioidosis. recombinant hcp2 protected 80% of mice against a lethal challenge with k96243, while recombinant hcp1, hcp3, and hcp6 protected 50% of mice against challenge. hcp6 was the onl ...201121300775
dna fingerprinting of septicemic and localized burkholderia pseudomallei isolates from malaysian patients.we have analysed dna fingerprinting patterns by pulsed-field gel electrophoresis (pfge) of 52 unrelated burkholderia pseudomallei strains isolated from septicemic and localized infections from malaysian subjects. a total of 38 pfge types were observed among 36 septicemic and 16 localized strains with no predominant pattern. type 25 was seen in 2 epidemiologically related strains, suggesting human to human transmission. twelve pfge types were shared among 26 strains (21 septicemic and 5 localized ...201121323173
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
dictyostelium discoideum as a model system for identification of burkholderia pseudomallei virulence factors.burkholderia pseudomallei is an emerging bacterial pathogen and category b biothreat. human infections with b. pseudomallei (called melioidosis) present as a range of manifestations, including acute septicemia and pneumonia. although melioidosis can be fatal, little is known about the molecular basis of b. pseudomallei pathogenicity, in part because of the lack of simple, genetically tractable eukaryotic models to facilitate en masse identification of virulence determinants or explore host-patho ...201121402765
complete killing of caenorhabditis elegans by burkholderia pseudomallei is dependent on prolonged direct association with the viable pathogen.burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis.201121408228
distinct roles for nitric oxide in resistant c57bl/6 and susceptible balb/c mice to control burkholderia pseudomallei infection.burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. we recently showed that nadph oxidase but not nitric oxide (no) contributes to resistance in innately resistant c57bl/6 mice in a b. pseudomallei respiratory infection model. however, the function of no for resistance was shown to differ among distinct strains of mice and proved also to be stage dependent in various infection models. the present study there ...201121410970
the burkholderia pseudomallei type iii secretion system and bopa are required for evasion of lc3-associated phagocytosis.burkholderia pseudomallei is the causative agent of melioidosis, a fatal infectious disease endemic in tropical regions worldwide, and especially prevalent in southeast asia and northern australia. this intracellular pathogen can escape from phagosomes into the host cytoplasm, where it replicates and infects adjacent cells. we previously demonstrated that, in response to b. pseudomallei infection of macrophage cell line raw 264.7, a subset of bacteria co-localized with the autophagy marker prote ...201121412437
development of reagents and assays for the detection of pathogenic burkholderia species.rapid detection of the category b biothreat agents burkholderia pseudomallei and burkholderia mallei in acute infections is critical to ensure that appropriate treatment is administered quickly to reduce an otherwise high probability of mortality (ca. 40% for b. pseudomallei). we are developing assays that can be used in clinical laboratories or security applications for the direct detection of surface-localized and secreted macromolecules produced by these organisms. we present our current medi ...201121413172
vith world melioidosis congress report: celebrating a century of research. 201121449838
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
evaluation of surrogate animal models of melioidosis.burkholderia pseudomallei is the gram-negative bacterial pathogen responsible for the disease melioidosis. b. pseudomallei establishes disease in susceptible individuals through multiple routes of infection, all of which may proceed to a septicemic disease associated with a high mortality rate. b. pseudomallei opportunistically infects humans and a wide range of animals directly from the environment, and modeling of experimental melioidosis has been conducted in numerous biologically relevant mo ...201021772830
melioidotic pericardial effusion.aim is to present a rare case of purulent pericardial effusion caused by burkholderia pseudomallei. pericardial sample was inoculated into bactec peds plus/f broth of the bactec automated system. after the system flagged positive, the broth was subjected to gram stain, biochemical tests and drug susceptibility. the organism was identified as burkholderia pseudomallei. tuberculosis (tb) is the most common cause of pericarditis in countries where it remains a major public health problem, but in th ...201022466500
melioidosis presenting as sepsis syndrome: a case report.melioidosis is an important disease in asia and australia. it is very rare in venezuela. we describe the case of a 50-year-old diabetic patient with several episodes of right tibial osteomyelitis, left shoulder arthritis, sternal osteomyelitis, right parietal osteomyelitis, and subperiosteal abscess, followed by septic arthritis of the right knee. in all cases gram stain smear showed gram-negative bacilli. culture yielded burkholderia pseudomallei, susceptible to third- and fourth-generation cep ...201021195650
genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen burkholderia pseudomallei k96243.burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. the bacterium is endemic to tropical regions, including south east asia and northern australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. b. pseudomallei is a gram-negative facultative intracellular pathogen that is able to replicate in macrophages. however despite the critical nature of its interaction with macrophages, ...201021203527
dna fingerprinting of human isolates of burkholderia pseudomallei from different geographical regions of malaysia.melioidosis is an infectious disease caused by burkholderia pseudomallei and endemic in southeast asia. one hundred and forty six clinical isolates of b. pseudomallei from different states in malaysia were obtained and molecular typing was carried out using pulsed-field gel electrophoresis (pfge). overall, nine clusters were successfully identified. burkholderia pseudomallei isolates used in this study were found to be genetically diverse and there were differences in the clusters of isolates fr ...201021399594
receptor mimicry as novel therapeutic treatment for biothreat agents.the specter of intentional release of pathogenic microbes and their toxins is a real threat. this article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. the minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the galβ1-4glcnac structure. the botulinum toxin serotypes a ...201021327124
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
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