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epidemiology of bacteremia caused by uncommon non-fermentative gram-negative bacteria.prevalence of bacteremia caused by non-fermentative gram-negative bacteria (nfgnb) has been increasing over the past decade. although many studies have already investigated epidemiology of nfgnb bacteremia, most focused only on common nfgnb including pseudomonas aeruginosa (pa) and acinetobacter baumannii (ab). knowledge of uncommon nfgnb bacteremia is very limited. our study aimed to investigate epidemiology and identify factors associated with uncommon nfgnb bacteremia.201323566113
multiple-antigen elisa for melioidosis--a novel approach to the improved serodiagnosis of melioidosis.burkholderia pseudomallei, the causative agent of melioidosis, is endemic to southeast asia and northern australia. clinical manifestations of disease are diverse, ranging from chronic infection to acute septicaemia. the current gold standard of diagnosis involves bacterial culture and identification which is time consuming and often too late for early medical intervention. hence, rapid diagnosis of melioidosis is crucial for the successful management of melioidosis.201323556548
systematic review and consensus guidelines for environmental sampling of burkholderia pseudomallei.burkholderia pseudomallei, a tier 1 select agent and the cause of melioidosis, is a gram-negative bacillus present in the environment in many tropical countries. defining the global pattern of b. pseudomallei distribution underpins efforts to prevent infection, and is dependent upon robust environmental sampling methodology. our objective was to review the literature on the detection of environmental b. pseudomallei, update the risk map for melioidosis, and propose international consensus guidel ...201323556010
bloodstream infection among adults in phnom penh, cambodia: key pathogens and resistance patterns.bloodstream infections (bsi) cause important morbidity and mortality worldwide. in cambodia, no surveillance data on bsi are available so far.201323555777
surprisingly low seroprevalence of burkholderia pseudomallei in exposed healthy adults in the darwin region of tropical australia where melioidosis is highly endemic.in the darwin region of australia where melioidosis is highly endemic, only 11/354 (3%) healthy residents were seropositive by indirect hemagglutination assay, despite extensive exposure to burkholderia pseudomallei. none developed melioidosis, but some described a prior self-limiting illness. this seropositivity rate is much lower than that seen in northeast thailand, where melioidosis is similarly highly endemic, potentially reflecting important differences between these two locations in the e ...201323536689
potential immunogenic polypeptides of burkholderia pseudomallei identified by shotgun expression library and evaluation of their efficacy for serodiagnosis of melioidosis.the search for novel immunogenic polypeptides to improve the accuracy and reliability of serologic diagnostic methods for burkholderia pseudomallei infection is ongoing. we employed a rapid and efficient approach to identify such polypeptides with sera from melioidosis patients using a small insert genomic expression library created from clinically confirmed local virulent isolates of b. pseudomallei. after 2 rounds of immunoscreening, 6 sero-positive clones expressing immunogenic peptides were ...201323532805
trimethoprim/sulfamethoxazole (co-trimoxazole) prophylaxis is effective against acute murine inhalational melioidosis and glanders.burkholderia pseudomallei is the causative agent of the disease melioidosis, which is prevalent in tropical countries and is intractable to a number of antibiotics. in this study, the antibiotic co-trimoxazole (trimethoprim/sulfamethoxazole) was assessed for the post-exposure prophylaxis of experimental infection in mice with b. pseudomallei and its close phylogenetic relative burkholderia mallei, the causative agent of glanders. co-trimoxazole was effective against an inhalational infection wit ...201323517714
development of burkholderia mallei and pseudomallei vaccines.burkholderia mallei and burkholderia pseudomallei are gram-negative bacteria that cause glanders and melioidosis, respectively. inhalational infection with either organism can result in severe and rapidly fatal pneumonia. inoculation by the oral and cutaneous routes can also produce infection. chronic infection may develop after recovery from acute infection with both agents, and control of infection with antibiotics requires prolonged treatment. symptoms for both meliodosis and glanders are non ...201323508691
new molecular interaction of iia(ntr) and hpr from burkholderia pseudomallei identified by x-ray crystallography and docking studies.the nitrogen-related phosphoenolpyruvate phosphotransferase system (pts(ntr) ) is involved in controlling ammonia assimilation and nitrogen fixation. the additional role of pts(ntr) as a regulatory link between nitrogen and carbon utilization in escherichia coli is assumed to be closely related to molecular functions of iia(ntr) in potassium homeostasis. we have determined the crystal structure of iia(ntr) from burkholderia pseudomallei (bpiia(ntr) ), which is a causative agent of melioidosis. t ...201323483653
clinical definitions of melioidosis.clinical definitions of melioidosis and inhalation-acquired melioidosis (burkholderia pseudomallei infection) are described together with the evidence used to develop these definitions. such definitions support accurate public health reporting, preparedness planning for deliberate b. pseudomallei release, design of experimental models, and categorization of naturally acquired melioidosis.201323468355
comparison of dna extraction kits for detection of burkholderia pseudomallei in spiked human whole blood using real-time pcr.burkholderia pseudomallei, the etiologic agent of melioidosis, is endemic in northern australia and southeast asia and can cause severe septicemia that may lead to death in 20% to 50% of cases. rapid detection of b. pseudomallei infection is crucial for timely treatment of septic patients. this study evaluated seven commercially available dna extraction kits to determine the relative recovery of b. pseudomallei dna from spiked edta-containing human whole blood. the evaluation included three manu ...201323460920
burkholderia pseudomallei infection in a healthy adult from a rural area of south india.melioidosis is an emerging disease producing protean manifestations, and is more common in alcoholics and diabetics. the disease can be a trivial localized lesion or a fatal septicemia. early diagnosis and appropriate antimicrobial treatment greatly reduces the mortality rate. we report a case of localized form of the disease in an elderly male with no known predisposing medical disease who responded well to oral amoxycillin-clavulanic acid and cotrimoxazole treatment.201223455813
impaired tlr5 functionality is associated with survival in melioidosis.melioidosis is infection caused by the flagellated saprophyte burkholderia pseudomallei. tlr5 is a pathogen recognition receptor activated by bacterial flagellin. we studied a genetic variant that encodes a defective tlr5 protein, tlr5(1174c)>t, to elucidate the role of tlr5 in melioidosis. we measured nf-κb activation induced by b. pseudomallei in human embryonic kidney-293 cells transfected with tlr5 and found that b. pseudomallei induced tlr5(1174c)- but not tlr5(1174t)-dependent activation o ...201323447684
importance of using bruker's security-relevant library for biotyper identification of burkholderia pseudomallei, brucella species, and francisella tularensis. 201323447635
activities of daily living associated with acquisition of melioidosis in northeast thailand: a matched case-control study.melioidosis is a serious infectious disease caused by the category b select agent and environmental saprophyte, burkholderia pseudomallei. most cases of naturally acquired infection are assumed to result from skin inoculation after exposure to soil or water. the aim of this study was to provide evidence for inoculation, inhalation and ingestion as routes of infection, and develop preventive guidelines based on this evidence.201323437412
multiplex qpcr for reliable detection and differentiation of burkholderia mallei and burkholderia pseudomallei.burkholderia mallei and b. pseudomallei are two closely related species of highly virulent bacteria that can be difficult to detect. pathogenic burkholderia are endemic in many regions worldwide and cases of infection, sometimes brought by travelers from unsuspected regions, also occur elsewhere. rapid, sensitive methods for identification of b. mallei and b. pseudomallei are urgently needed in the interests of patient treatment and epidemiological surveillance.201323409683
disseminated melioidosis presenting as septic arthritis.melioidosis is an infection caused by burkholderia pseudomallei. the disease is known as a remarkable imitator due to the wide and variable clinical spectrum of its manifestations. septic arthritis is rare but well-recognized manifestation of this disease. we report a case of melioidosis in a 52 year male with uncontrolled diabetes mellitus (dm) presenting with a rare combination of septic arthritis and abscesses in the chest wall, liver and subcutaneous tissue. the patient responded to prolonge ...201223409422
a heterodimer comprised of two bovine lactoferrin antimicrobial peptides exhibits powerful bactericidal activity against burkholderia pseudomallei.melioidosis is a severe infectious disease that is endemic in southeast asia and northern australia. burkholderia pseudomallei, the causative agent of this disease, has developed resistance to an increasing list of antibiotics, demanding a search for novel agents. lactoferricin and lactoferrampin are two antimicrobial domains of lactoferrin with a broad spectrum of antimicrobial activity. a hybrid peptide (lfchimera) containing lactoferrampin (lfampin265-284) and a part of lactoferricin (lfcin17 ...201323404819
galleria mellonella as a model system to test the pharmacokinetics and efficacy of antibiotics against burkholderia pseudomallei.mammalian models of infection are paramount to elucidating the mechanisms of bacterial pathogenesis and are also used for evaluating the efficacy of novel antimicrobials before the commencement of human trials. in this study, galleria mellonella was used to determine the efficacy of antibiotics towards a burkholderia thailandensis infection in g. mellonella larvae. kanamycin, imipenem, ceftazidime, doxycycline and ciprofloxacin could all provide some protection when given 1 h before challenge wi ...201323402703
an assessment of common marmoset (callithrix jacchus) γ9(+) t cells and their response to phosphoantigen in vitro.γ9δ2 t cells are a primate-specific γδ t cell subtype that expand and become activated during infection, responding directly to phosphoantigens which are by-products of essential metabolic pathways in both bacteria and mammals. analogues of natural phosphoantigens have been developed as potential immunotherapeutics for treatment of tumours and infectious diseases. several non-human primate models have been used in preclinical studies, however, little is known about marmoset γ9δ2 t cell responses ...201223399838
burkholderia pseudomallei osteomyelitis of the metatarsal in an infant.burkoholderia pseudomallei is an emerging cause of localized musculoskeletal infections. we report the case of a 9-month-old infant with isolated primary chronic osteomyelitis of the fifth metatarsal. radiographs showed expansion and thickening of the cortex. the metatarsal had lytic lesions with scalloped margins; no periosteal reaction or sequestration was seen. surgical debridement provided removal of infected material and adequate drainage by saucerization. b. pseudomallei was isolated from ...201323395629
burkholderia vaccines: are we moving forward?the genus burkholderia consists of diverse species which includes both "friends" and "foes." some of the "friendly" burkholderia spp. are extensively used in the biotechnological and agricultural industry for bioremediation and biocontrol. however, several members of the genus including b. pseudomallei, b. mallei, and b. cepacia, are known to cause fatal disease in both humans and animals. b. pseudomallei and b. mallei are the causative agents of melioidosis and glanders, respectively, while b. ...201323386999
host responses to melioidosis and tuberculosis are both dominated by interferon-mediated signaling.melioidosis (burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in northeast thailand and northern australia. b. pseudomallei is a soil saprophyte endemic to southeast asia and northern australia. the clinical presentation of melioidosis may mimic tuberculosis (both cause chronic suppurative lesions unresponsive to conventional antibiotics and both commonly affect the lungs). the two diseases have overlapping risk profiles (e.g., diabetes, corticosteroid use), an ...201323383015
survival, sublethal injury, and recovery of environmental burkholderia pseudomallei in soil subjected to desiccation.environmental burkholderia pseudomallei isolated from sandy soil at castle hill, townsville, in the dry tropic region of queensland, australia, was inoculated into sterile-soil laboratory microcosms subjected to variable soil moisture. survival and sublethal injury of the b. pseudomallei strain were monitored by recovery using culture-based methods. soil extraction buffer yielded higher recoveries as an extraction agent than sterile distilled water. b. pseudomallei was not recoverable when inocu ...201323377947
efficacy of post exposure administration of doxycycline in a murine model of inhalational melioidosis.burkholderia pseudomallei is the causative agent of melioidosis. treatment of melioidosis is suboptimal and developing improved melioidosis therapies requires animal models. in this report, we exposed male balb/c mice to various amounts of aerosolized b. pseudomallei 1026b to determine lethality. after establishing a median lethal dose (ld(50)) of 2,772 colony forming units (cfu)/animal, we tested the ability of doxycycline administered 6 hours after exposure to a uniformly lethal dose of ~20 ld ...201323359492
characterisation of predominant molecular patterns of burkholderia pseudomallei in taiwan.the soil-dwelling pathogen burkholderia pseudomallei is the cause of melioidosis. in this study, the geographical and temporal distributions of predominant molecular patterns occurring in clinical and environmental isolates of b. pseudomallei were characterised.201323355636
epidemiology, microbiology and mortality associated with community-acquired bacteremia in northeast thailand: a multicenter surveillance study.national statistics in developing countries are likely to underestimate deaths due to bacterial infections. here, we calculated mortality associated with community-acquired bacteremia (cab) in a developing country using routinely available databases.201323349954
characterization of bcaa, a putative classical autotransporter protein in burkholderia pseudomallei.burkholderia pseudomallei is a tier 1 select agent, and the causative agent of melioidosis, a disease with effects ranging from chronic abscesses to fulminant pneumonia and septic shock, which can be rapidly fatal. autotransporters (ats) are outer membrane proteins belonging to the type v secretion system family, and many have been shown to play crucial roles in pathogenesis. the open reading frame bp1026b_ii1054 (bcaa) in b. pseudomallei strain 1026b is predicted to encode a classical autotrans ...201323340315
novel gain of function approaches for vaccine candidate identification in burkholderia pseudomallei.the gram-negative bacterium burkholderia pseudomallei is a serious environmental pathogen and the causative agent of the often fatal melioidosis. disease occurs following exposure to contaminated water or soil, usually through cuts in the skin or via inhalation. however, the underlying mechanisms of pathogenicity remain poorly understood. b. pseudomallei is endemic to south east asia and northern australia where infections are associated with antibiotic resistance and high mortality rates. categ ...201223316481
case report of orbital cellulitis and necrotizing fasciitis from melioidosis.a 48-year-old thai male farmer presented with progressive swelling of the right eyelid and high-grade fever. his visual acuity declined and the right side of his forehead developed a necrotic skin lesion with a purulent discharge. ct of the orbits suggested orbital cellulitis with subperiosteal abscess. intravenous ceftriaxone and clindamycin were given empirically but then switched to vancomycin and meropenem because of rapid deterioration together with clinical sepsis. burkholderia pseudomalle ...201623303132
does hiv status affect the aetiology, bacterial resistance patterns and recommended empiric antibiotic treatment in adult patients with bloodstream infection in cambodia?the microbiologic causes of bloodstream infections (bsi) may differ between hiv-positive and hiv-negative patients and direct initial empiric antibiotic treatment (i.e. treatment before culture results are available). we retrospectively assessed community-acquired bsi episodes in adults in cambodia according to hiv status for spectrum of bacterial pathogens, antibiotic resistance patterns and appropriateness of empiric antibiotics.201323294446
burkholderia mallei and burkholderia pseudomallei stimulate differential inflammatory responses from human alveolar type ii cells (atii) and macrophages.alveolar type ii pneumocytes (atii) and alveolar macrophages (am) play a crucial role in the lung's innate immune response. burkholderia pseudomallei (bp) and burkholderia mallei (bm) are facultative gram-negative bacilli that cause melioidosis and glanders, respectively. the inhalation of these pathogens can cause lethal disease and death in humans. we sought to compare the pathogenesis of and host responses to bp and bm through contact with human primary atii cells and monocytes-derived macrop ...201223293773
computational discovery and rt-pcr validation of novel burkholderia conserved and burkholderia pseudomallei unique srnas.the srnas of bacterial pathogens are known to be involved in various cellular roles including environmental adaptation as well as regulation of virulence and pathogenicity. it is expected that srnas may also have similar functions for burkholderia pseudomallei, a soil bacterium that can adapt to diverse environmental conditions, which causes the disease melioidosis and is also able to infect a wide variety of hosts.201223282220
melioidosis and the kidney.melioidosis, caused by the saprophytic soil and freshwater gram-negative aerobic bacillus burkholderia pseudomallei, is classically characterized by pneumonia, sometimes with multiple organ abscesses, usually in patients with defined risk factors and with a mortality rate of up to 40%. it is a major cause of community-acquired sepsis in southeast asia and tropical northern australia with an expanding global geographical distribution. it is increasingly recognized as an opportunistic infectious d ...201323279670
bacteraemias in tropical australia: changing trends over a 10-year period.bacteraemia is an important cause of morbidity and mortality worldwide. this is the largest reported study of bacteraemias in australia. the presence of organisms endemic to the tropical region and the changing trends described have significant implications for empirical antibiotic therapy. this retrospective study examined 8976 blood cultures from townsville hospital, a regional australian hospital located in the tropics over a 10-year period. the rate of bacteraemic episodes during the study p ...201223276769
expression and characterization of an iron-containing superoxide dismutase from burkholderia pseudomallei.a superoxide dismutase (sod) gene from burkholderia pseudomallei, the causative agent of melioidosis, was cloned and expressed in escherichia coli, and its product was functionally and physically characterized. the gene has an open-reading frame of 579 bp. the deduced amino acid sequence has 192 residues with a calculated molecular mass of ~22 kda. sequence comparison with other bacterial sods showed that the protein contains typical metal-binding motifs and other fe-sod-conserved residues. the ...201223274991
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
a non-invasive intratracheal inoculation method for the study of pulmonary melioidosis.pulmonary melioidosis, a disease manifestation caused by the bacterium burkholderia pseudomallei, has been studied using aerosols or intranasal (in) inoculation in small animal models. both have inherent disadvantages which may not accurately model primary pulmonary melioidosis in humans. intratracheal inoculation (it) by direct visualization of the tracheal opening offers an alternative technique for infection that overcomes the disadvantages of aerosol and in challenge. in this study, we descr ...201223267442
growth inhibition of pathogenic bacteria by sulfonylurea herbicides.emerging resistance to current antibiotics raises the need for new microbial drug targets. we show that targeting branched-chain amino acid (bcaa) biosynthesis using sulfonylurea herbicides, which inhibit the bcaa biosynthetic enzyme acetohydroxyacid synthase (ahas), can exert bacteriostatic effects on several pathogenic bacteria, including burkholderia pseudomallei, pseudomonas aeruginosa, and acinetobacter baumannii. our results suggest that targeting biosynthetic enzymes like ahas, which are ...201223263008
capsule influences the deposition of critical complement c3 levels required for the killing of burkholderia pseudomallei via nadph-oxidase induction by human neutrophils.burkholderia pseudomallei is the causative agent of melioidosis and is a major mediator of sepsis in its endemic areas. because of the low ld(50) via aerosols and resistance to multiple antibiotics, it is considered a tier 1 select agent by the cdc and aphis. b. pseudomallei is an encapsulated bacterium that can infect, multiply, and persist within a variety of host cell types. in vivo studies suggest that macrophages and neutrophils are important for controlling b. pseudomallei infections, howe ...201223251706
structural basis of toxicity and immunity in contact-dependent growth inhibition (cdi) systems.contact-dependent growth inhibition (cdi) systems encode polymorphic toxin/immunity proteins that mediate competition between neighboring bacterial cells. we present crystal structures of cdi toxin/immunity complexes from escherichia coli ec869 and burkholderia pseudomallei 1026b. despite sharing little sequence identity, the toxin domains are structurally similar and have homology to endonucleases. the ec869 toxin is a zn(2+)-dependent dnase capable of completely degrading the genomes of target ...201223236156
mexxy multidrug efflux system of pseudomonas aeruginosa.anti-pseudomonas aminoglycosides, such as amikacin and tobramycin, are used in the treatment of pseudomonas aeruginosa infections. however, their use is linked to the development of resistance. during the last decade, the mexxy multidrug efflux system has been comprehensively studied, and numerous reports of laboratory and clinical isolates have been published. this system has been increasingly recognized as one of the primary determinants of aminoglycoside resistance in p. aeruginosa. in p. aer ...201223233851
mechanisms of antibiotic resistance in burkholderia pseudomallei: implications for treatment of melioidosis.burkholderia pseudomallei is the etiologic agent of melioidosis. this multifaceted disease is difficult to treat, resulting in high morbidity and mortality. treatment of b. pseudomallei infections is lengthy and necessitates an intensive phase (parenteral ceftazidime, amoxicillin-clavulanic acid or meropenem) and an eradication phase (oral trimethoprim-sulfamethoxazole). the main resistance mechanisms affecting these antibiotics include enzymatic inactivation, target deletion and efflux from the ...201223231488
φx216, a p2-like bacteriophage with broad burkholderia pseudomallei and b. mallei strain infectivity.burkholderia pseudomallei and b. mallei are closely related category b select agents of bioterrorism and the causative agents of the diseases melioidosis and glanders, respectively. rapid phage-based diagnostic tools would greatly benefit early recognition and treatment of these diseases. there is extensive strain-to-strain variation in b. pseudomallei genome content due in part to the presence or absence of integrated prophages. several phages have previously been isolated from b. pseudomallei ...201223217012
endogenous protein c has a protective role during gram-negative pneumosepsis (melioidosis).activated protein c (apc) exerts anticoagulant effects via inactivation of factors va and viiia and cytoprotective effects via protease activated receptor (par)1. inhibition of endogenous apc in endotoxemia and sepsis results in exacerbation of coagulation and inflammation, with consequent enhanced lethality.201323216621
intoxication vs. infection: a decade of studying burkholderia pseudomallei virulence in a simple infection model. 201223211680
burkholderia thailandensis is virulent in drosophila melanogaster.melioidosis is a serious infectious disease endemic to southeast asia and northern australia. this disease is caused by the gram-negative bacterium burkholderia pseudomallei; burkholderia thailandensis is a closely-related organism known to be avirulent in humans. b. thailandensis has not previously been used to infect drosophila melanogaster. we examined the effect of b. thailandensis infection on fly survival, on antimicrobial peptide expression, and on phagocytic cells. in the fruit fly, whic ...201223209596
impaired early cytokine responses at the site of infection in a murine model of type 2 diabetes and melioidosis comorbidity.bacterial infections are a common and serious complication of type 2 diabetes (t2d). the prevalence of melioidosis, an emerging tropical infection caused by the gram-negative bacterium burkholderia pseudomallei, is increased in people with t2d. this is the first study to compare murine models of t2d and melioidosis. susceptibility and disease progression following infection with b. pseudomallei were compared in our diet-induced polygenic mouse model and a leptin receptor-deficient monogenic mode ...201323208607
glycogen synthase kinase-3β inhibition improved survivability of mice infected with burkholderia pseudomallei.the disease melioidosis, caused by the soil bacteria burkholderia pseudomallei, often manifests as acute septicemia with high fatality. glycogen synthase kinase-3β (gsk3β) plays a key role during the inflammatory response induced by bacteria. we used a murine model of acute melioidosis to investigate the effects of licl, a gsk3 inhibitor on experimental animal survivability as well as tnf-α, il-1β, ifn-γ, il-10 and il-1ra cytokine levels in blood, lung, liver and spleen of b. pseudomallei-infect ...201223202600
a preliminary x-ray study of transketolase from burkholderia pseudomallei.tkta is the most critical enzyme in the nonoxidative pentose phosphate pathway. it catalyzes the conversion of xylulose 5-phosphate and ribose 5-phosphate into sedoheptulose 7-phosphate and glyceraldehyde 3-phosphate, and its products are used in the biosynthesis of acetyl-coa, aromatic amino acids, nucleic acids and adp-l-glycero-β-d-manno-heptose. tkta also has an unexpected role in chromosome structure that is independent of its metabolic responsibilities. therefore, it is a new potent antibi ...201223192046
elisa and immuno-polymerase chain reaction assays for the sensitive detection of melioidosis.melioidosis is caused by the gram-negative bacterium burkholderia pseudomallei. the gold standard for diagnosis is culture, which requires at least 3-4 days to obtain a result, hindering successful treatment of acute disease. an indirect haemagglutination assay (iha) is often used but lacks sensitivity. approximately half of patients later confirmed culture positive are not detected by iha at presentation and a subset of patients persistently continue to be iha negative. more rapid and reliable ...201323177220
structural mechanism of ubiquitin and nedd8 deamidation catalyzed by bacterial effectors that induce macrophage-specific apoptosis.targeting eukaryotic proteins for deamidation modification is increasingly appreciated as a general bacterial virulence mechanism. here, we present an atomic view of how a bacterial deamidase effector, cycle-inhibiting factor homolog in burkholderia pseudomallei (chbp), recognizes its host targets, ubiquitin (ub) and ub-like neural precursor cell expressed, developmentally down-regulated 8 (nedd8), and catalyzes site-specific deamidation. crystal structures of chbp-ub/nedd8 complexes show that u ...201223175788
workshop on treatment of and postexposure prophylaxis for burkholderia pseudomallei and b. mallei infection, 2010.the us public health emergency medical countermeasures enterprise convened subject matter experts at the 2010 hhs burkholderia workshop to develop consensus recommendations for postexposure prophylaxis against and treatment for burkholderia pseudomallei and b. mallei infections, which cause melioidosis and glanders, respectively. drugs recommended by consensus of the participants are ceftazidime or meropenem for initial intensive therapy, and trimethoprim/sulfamethoxazole or amoxicillin/clavulan ...201223171644
melioidosis--an uncommon but also under-recognized cause of pneumonia in papua new guinea.melioidosis is being increasingly recognized as an important cause of severe, acute community-acquired pneumonia in various tropical regions. the chronic form of melioidosis can also mimic tuberculosis. studies have established that, while uncommon in the port moresby region, melioidosis is an important cause of pneumonia and sepsis in the balimo region of western province. phylogenetic analyses of strains of burkholderia pseudomallei from papua new guinea have shown them to be more closely rela ...201223163189
potential of recombinant flagellin fragment from burkholderia thailandensis as an antigen for melioidosis antibody detection by indirect elisa.non-pathogenic burkholderia thailandensis may be used as a model for burkholderia pseudomallei due to the genetic similarity of these species. moreover, the experimental manipulation of b. thailandensis is safer. in this study, we constructed recombinant flagellin protein fragments of b. thailandensis e264 (flag300, flag600, flag900, and flagfl fragments) and used fragments as the antigen to detect melioidosis antibodies by an indirect enzyme-linked immunosorbent assay (indirect elisa). the seru ...201323159530
a structure-based strategy for epitope discovery in burkholderia pseudomallei oppa antigen.we present an approach integrating structural and computational biology with immunological tests to identify epitopes in the oppa antigen from the gram-negative pathogen burkholderia pseudomallei, the etiological agent of melioidosis. the crystal structure of oppa(bp), reported here at 2.1 å resolution, was the basis for a computational analysis that identified three potential epitopes. in parallel, antigen proteolysis and immunocapturing allowed us to identify three additional peptides. all six ...201323159127
first genome sequence of a burkholderia pseudomallei isolate in china, strain bpc006, obtained from a melioidosis patient in hainan.melioidosis, caused by burkholderia pseudomallei, is considered to be endemic to northern australia and southeast asia, with high mortality and relapse rates, regardless of powerful antibiotic therapy. here we report the first genome sequence of burkholderia pseudomallei strain bpc006, obtained from a melioidosis patient in hainan, china. the genome sizes of the 2 chromosomes were determined to be 4,001,777 bp and 3,153,284 bp.201223144371
murine pulmonary infection and inflammation induced by inhalation of burkholderia pseudomallei.melioidosis is a tropical disease caused by ingestion, percutaneous inoculation or inhalation of the gram-negative soil saprophyte burkholderia pseudomallei. we developed a reproducible experimental murine model of pneumonic melioidosis induced by inhalation of aerosolized b. pseudomallei 1026b. in a series of experiments performed to bracket the lethal dose, we found that c57bl/6 mice were modestly more resistant than balb/c mice (median lethal dose 334 cfu/lung vs 204 cfu/lung). we further cha ...201223136994
detection of burkholderia pseudomallei o-antigen serotypes in near-neighbor species.burkholderia pseudomallei is the etiological agent of melioidosis and a cdc category b select agent with no available effective vaccine. previous immunizations in mice have utilized the lipopolysaccharide (lps) as a potential vaccine target because it is known as one of the most important antigenic epitopes in b. pseudomallei. complicating this strategy are the four different b. pseudomallei lps o-antigen types: a, b, b2, and rough. sero-crossreactivity is common among o-antigens of burkholderia ...201223126230
beclin 1 is required for starvation-enhanced, but not rapamycin-enhanced, lc3-associated phagocytosis of burkholderia pseudomallei in raw 264.7 cells.lc3-associated phagocytosis (lap) of burkholderia pseudomallei by murine macrophage (raw 264.7) cells is an intracellular innate defense mechanism. beclin 1, a protein with several roles in autophagic processes, is known to be recruited to phagosomal membranes as a very early event in lap. we sought to determine whether knockdown of beclin 1 by small interfering rna (sirna) would affect recruitment of lc3 and subsequent lap of infecting b. pseudomallei. both starvation and rapamycin treatment ca ...201323115045
identification of type ii toxin-antitoxin modules in burkholderia pseudomallei.type ii toxin-antitoxin (ta) systems are believed to be widely distributed amongst bacteria although their biological functions are not clear. we have identified eight candidate ta systems in the genome of the human pathogen burkholderia pseudomallei. five of these were located in genome islands. of the candidate toxins, bpsl0175 (rele1) or bpss1060 (rele2) caused growth to cease when expressed in escherichia coli, whereas expression of bpss0390 (hica) or bpss1584 (hipa) (in an e. coli δhipba ba ...201323082999
tn5-ot182 should not be used to identify genes involved in biofilm formation in burkholderia pseudomallei.burkholderia pseudomallei, a gram-negative bacterium, is the causative agent of melioidosis. one of the important virulence properties of this bacteria is its ability to form a biofilm. genes involved in biofilm formation in b. pseudomallei have not been thoroughly studied. in this study, tn5-ot182 mutagenesis was used to isolate of b. pseudomallei strain a2 mutants unable to produce biofilm. ten biofilm-defective transposon mutants were isolated and analyzed. flanking dna from each transposon m ...201223082562
outbreak of melioidosis and leptospirosis co-infection following a rescue operation.we analyzed the epidemiological data of all people who were involved in the search and rescue operation in lubuk yu, a natural recreational forest with waterfall and stream. the hospital admission records of the cases who fulfilled the case definition and the environmental samples result taken at lubuk yu recreational area were studied. 153 people were exposed to this outbreak, 85 (55.5%) were professional rescuers from various government agencies and 68 (44.5%) were villagers. 21 fulfilled the ...201223082420
burkholderia pseudomallei kills caenorhabditis elegans through virulence mechanisms distinct from intestinal lumen colonization.the nematode caenorhabditis elegans is hypersusceptible to burkholderia pseudomallei infection. however, the virulence mechanisms underlying rapid lethality of c. elegans upon b. pseudomallei infection remain poorly defined. to probe the host-pathogen interaction, we constructed gfp-tagged b. pseudomallei and followed bacterial accumulation within the c. elegans intestinal lumen. contrary to slow-killing by most bacterial pathogens, b. pseudomallei caused fairly limited intestinal lumen coloniza ...201223076282
distinct human antibody response to the biological warfare agent burkholderia mallei.the genetic similarity between burkholderia mallei (glanders) and burkholderia pseudomallei (melioidosis) had led to the general assumption that pathogenesis of each bacterium would be similar. in 2000, the first human case of glanders in north america since 1945 was reported in a microbiology laboratory worker. leveraging the availability of pre-exposure sera for this individual and employing the same well-characterized protein array platform that has been previously used to study a large cohor ...201223076276
construction and characterization of a burkholderia pseudomallei wzm deletion mutant.in burkholderia pseudomallei, the pathogen that causes melioidosis, the gene cluster encoding the capsular polysaccharide, is located on chromosome 1. among the 19 capsular genes in this cluster, wzm has not been thoroughly studied. to study the function of wzm, we generated a deletion mutant and compared it with the wild-type strain. the mutant produced less biofilm in minimal media and was more sensitive to desiccation and oxidative stress compared with the wild-type strain, indicating that wz ...201223075783
an objective approach for burkholderia pseudomallei strain selection as challenge material for medical countermeasures efficacy testing.burkholderia pseudomallei is the causative agent of melioidosis, a rare disease of biodefense concern with high mortality and extreme difficulty in treatment. no human vaccines are available that protect against b. pseudomallei infection, and with the current limitations of antibiotic treatment, the development of new preventative and therapeutic interventions is crucial. although clinical trials could be used to test the efficacy of new medical countermeasures (mcms), the high mortality rates a ...201223057010
rapid identification of burkholderia mallei and burkholderia pseudomallei by intact cell matrix-assisted laser desorption/ionisation mass spectrometric typing.burkholderia (b.) pseudomallei and b. mallei are genetically closely related species. b. pseudomallei causes melioidosis in humans and animals, whereas b. mallei is the causative agent of glanders in equines and rarely also in humans. both agents have been classified by the cdc as priority category b biological agents. rapid identification is crucial, because both agents are intrinsically resistant to many antibiotics. matrix-assisted laser desorption/ionisation mass spectrometry (maldi-tof ms) ...201223046611
a traveller presenting with severe melioidosis complicated by a pericardial effusion: a case report.burkholderia pseudomallei, the etiologic agent of melioidosis, is endemic to tropic regions, mainly in southeast asia and northern australia. melioidosis occurs only sporadically in travellers returning from disease-endemic areas. severe clinical disease is seen mostly in patients with alteration of immune status. in particular, pericardial effusion occurs in 1-3% of patients with melioidosis, confined to endemic regions. to our best knowledge, this is the first reported case of melioidosis in a ...201223035948
cranial melioidosis with extradural extension after a fall in the bathroom.a 32-year-old diabetic male, with a past history of head injury and seizures, presented with a painful swelling over his forehead present for the past three months. cranial mri demonstrated the presence of a scalp collection with extradural extension through a bony defect. biopsy from the area showed caseating necrosis suggestive of tuberculosis. although the patient failed to return for initiation of anti-tubercular therapy for the next 11 months, the swelling did not progress, and there were n ...201223024720
bacterial gene loss as a mechanism for gain of antimicrobial resistance.acquisition of exogenous dna by pathogenic bacteria represents the basis for much of the acquired antimicrobial resistance in pathogenic bacteria. a more extreme mechanism to avoid the effect of an antibiotic is to delete the drug target, although this would be predicted to be rare since drug targets are often essential genes. here, we review and discuss the description of a novel mechanism of resistance to the cephalosporin drug ceftazidime caused by loss of a penicillin-binding protein (pbp) i ...201223022568
evaluation of six commercial dna extraction kits for recovery of burkholderia pseudomallei dna.six commercially available dna extraction kits, as well as thermal lysis and proteinase k dna extraction were evaluated regarding bacterial inactivation, dna yield and purity, and their use in a burkholderia pseudomallei real-time pcr. while all methods successfully inactivated the bacteria, by measuring dna purity and the level of detection by real-time pcr, the proteinase k method was the most sensitive.201223022447
transverse myelitis secondary to melioidosis: a case report.melioidosis has become an emerging infection in sri lanka; a country which is considered non endemic for it. paraplegia due to burkholderia pseudomallei is a very rare entity encountered even in countries where the disease is endemic. there are no reported cases of transverse myelitis due to melioidosis in sri lankan population thus we report the first case.201223020820
thoracic radiologic manifestations of melioidosis.melioidosis (burkholderia pseudomallei) is a gram-negative bacterial infection that is highly endemic in southeast asia and oceania. pulmonary disease is the most common form of involvement. the clinical-radiologic thoracic manifestations of melioidosis can be classified as acute, subacute, subclinical, and chronic forms. radiographic findings include nodular, alveolar, or mixed infiltration/consolidation with or without cavities. pleural effusion, pneumothorax, and pericardial involvement can b ...201623009770
identification and evaluation of twin-arginine translocase inhibitors.the twin-arginine translocase (tat) in some bacterial pathogens, including pseudomonas aeruginosa, burkholderia pseudomallei, and mycobacterium tuberculosis, contributes to pathogenesis by translocating extracellular virulence determinants across the inner membrane into the periplasm, thereby allowing access to the xcp (type ii) secretory system for further export in gram-negative organisms, or directly to the outside surface of the cell, as in m. tuberculosis. tat-mediated secretion appreciably ...201223006747
involvement of signal regulatory protein α, a negative regulator of toll-like receptor signaling, in impairing the myd88-independent pathway and intracellular killing of burkholderia pseudomallei-infected mouse macrophages.the facultative intracellular gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis and is known for its ability to evade the toll-like receptor (tlr)-mediated innate immune response. previously it has been demonstrated that this bacterium was able to suppress the myd88-independent pathway and can survive macrophage intracellular killing. however, the underlying mechanisms responsible for the suppression of this pathway are not fully understood. in the present s ...201222988019
development of ceftazidime resistance in an acute burkholderia pseudomallei infection.burkholderia pseudomallei, a bacterium that causes the disease melioidosis, is intrinsically resistant to many antibiotics. first-line antibiotic therapy for treating melioidosis is usually the synthetic β-lactam, ceftazidime (caz), as almost all b. pseudomallei strains are susceptible to this drug. however, acquired caz resistance can develop in vivo during treatment with caz, which can lead to mortality if therapy is not switched to a different drug in a timely manner. serial b. pseudomallei i ...201222977307
mapping the aetiology of non-malarial febrile illness in southeast asia through a systematic review--terra incognita impairing treatment policies.an increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of ability of many health systems to manage other causes of febrile disease. a lack of knowledge of distribution of these pathogens, and a lack of screening and point-of-care diagnostics to identify them, prevents effective management of these generally treatable contributors to disease burden. while prospective data collection is v ...201222970193
the effect of environmental conditions on biofilm formation of burkholderia pseudomallei clinical isolates.burkholderia pseudomallei, a gram-negative saprophytic bacterium, is the causative agent of the potentially fatal melioidosis disease in humans. in this study, environmental parameters including temperature, nutrient content, ph and the presence of glucose were shown to play a role in in vitro biofilm formation by 28 b. pseudomallei clinical isolates, including four isolates with large colony variants (lcvs) and small colony variants (scvs) morphotypes. enhanced biofilm formation was observed wh ...201222970167
production of interleukin-27 by human neutrophils regulates their function during bacterial infection.septicemia is the most severe form of melioidosis caused by the gram-negative bacterium, burkholderia pseudomallei. here, we show that levels of il-27p28 transcript and protein were both significantly elevated in patients with sepsis, particularly melioidosis and in patients with unfavorable disease outcome. moreover, human monocytes/macrophages and neutrophils were the major source of il-27 during infection. the addition of exogenous il-27 in vitro resulted in significantly increased bacterial ...201222965735
neutrophil extracellular traps exhibit antibacterial activity against burkholderia pseudomallei and are influenced by bacterial and host factors.burkholderia pseudomallei is the causative pathogen of melioidosis, of which a major predisposing factor is diabetes mellitus. polymorphonuclear neutrophils (pmns) kill microbes extracellularly by the release of neutrophil extracellular traps (nets). pmns play a key role in the control of melioidosis, but the involvement of nets in killing of b. pseudomallei remains obscure. here, we showed that bactericidal nets were released from human pmns in response to b. pseudomallei in a dose- and time-de ...201222927051
particle-size dependent effects in the balb/c murine model of inhalational melioidosis.deposition of burkholderia pseudomallei within either the lungs or nasal passages of the balb/c murine model resulted in different infection kinetics. the infection resulting from the inhalation of b. pseudomallei within a 12 μm particle aerosol was prolonged compared to a 1 μm particle aerosol with a mean time-to-death (mtd) of 174.7 ± 14.9 h and 73.8 ± 11.3 h, respectively. inhalation of b. pseudomallei within 1 μm or 12 μm particle aerosols resulted in a median lethal dose (mld) of 4 and 12 c ...201222919690
immunogenic recombinant burkholderia pseudomallei mpra serine protease elicits protective immunity in mice.burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. as therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. in an earlier study, we reported on the b. pseudomallei serine mpra protease, which is relatively stable over a wide ph and temperature range and digests physiological proteins. the present study ...201222919676
development and characterization of a caprine aerosol infection model of melioidosis.infection with burkholderia pseudomallei causes the disease melioidosis, which often presents as a serious suppurative infection that is typically fatal without intensive treatment and is a significant emerging infectious disease in southeast asia. despite intensive research there is still much that remains unknown about melioidosis pathogenesis. new animal models of melioidosis are needed to examine novel aspects of pathogenesis as well as for the evaluation of novel therapeutics. the objective ...201222916225
development of capsular polysaccharide-based glycoconjugates for immunization against melioidosis and glanders.burkholderia pseudomallei and burkholderia mallei, the etiologic agents of melioidosis and glanders, respectively, cause severe disease in humans and animals and are considered potential agents of biological warfare and terrorism. diagnosis and treatment of infections caused by these pathogens can be challenging and, in the absence of chemotherapeutic intervention, acute disease is frequently fatal. at present, there are no human or veterinary vaccines available for immunization against these em ...201222912938
burkholderia pseudomallei osteomyelitis: an unusual cause of fever in a returned traveller.a 52-year-old diabetic man presented to the emergency department with a history of fevers and pain in his right thigh. he had recently returned from a 10-month trip to vietnam. a suspected bacterial abscess in the right thigh did not respond to empirical antibiotics. subsequent investigations revealed melioidotic osteomyelitis of the femur. this case emphasises the need to consider the diagnosis of melioidosis in patients presenting with fever following travel in endemic areas.201222905056
the madagascar hissing cockroach as a novel surrogate host for burkholderia pseudomallei, b. mallei and b. thailandensis.burkholderia pseudomallei and burkholderia mallei are gram-negative pathogens responsible for the diseases melioidosis and glanders, respectively. both species cause disease in humans and animals and have been designated as category b select agents by the centers for disease control and prevention (cdc). burkholderia thailandensis is a closely related bacterium that is generally considered avirulent for humans. while it can cause disease in rodents, the b. thailandensis 50% lethal dose (ld50) is ...201222892068
crystallization and preliminary x-ray analysis of the receiver domain of a putative response regulator, bpsl0128, from burkholderia pseudomallei.bpsl0128, a gene encoding a putative response regulator from burkholderia pseudomallei strain d286, has been cloned into a petblue-1 vector system, overexpressed in escherichia coli and purified. the full-length protein is degraded during purification to leave a fragment corresponding to the putative receiver domain, and crystals of this protein that diffracted to beyond 1.75 å resolution have been grown by the hanging-drop vapour-diffusion technique using peg 6000 as the precipitant. the crysta ...201222869122
molecular investigation of virulence determinants between a virulent clinical strain and an attenuated strain of burkholderia pseudomallei.burkholderia pseudomallei is the causative agent of melioidosis. we initiated this investigation with a virulent and an attenuated strain of b. pseudomallei. pulsed-field gel electrophoresis was carried out initially for macrogenomic comparison of both strains of b. pseudomallei. however, the pulsotypes obtained were identical and therefore we applied a subtractive hybridization technique to distinguish and determine the possible differences between the two strains. six virulence strain-specific ...201222846664
burkholderia pseudomallei transcriptional adaptation in macrophages.burkholderia pseudomallei is a facultative intracellular pathogen of phagocytic and non-phagocytic cells. how the bacterium interacts with host macrophage cells is still not well understood and is critical to appreciate the strategies used by this bacterium to survive and how intracellular survival leads to disease manifestation.201222823543
misidentification of burkholderia pseudomallei as burkholderia cepacia by the vitek 2 system.a previously healthy chinese male returned from working in the malaysian jungle with a fever. a blood culture grew gram-negative bacilli that were initially identified as burkholderia cepacia by the vitek 2 system but were subsequently found to be burkholderia pseudomallei by partial sequencing of the 16s rrna gene. the identification of b. pseudomallei using commercially available automated systems is problematic and clinicians in non-endemic areas should be aware of the possibility of melioido ...201222820689
blf1, the first burkholderia pseudomallei toxin, connects inhibition of host protein synthesis with melioidosis.melioidosis is a disease caused by infection with burkholderia pseudomallei. the molecular basis for the pathogenicity of b. pseudomallei is poorly understood. however, recent work has identified the first toxin from this bacterium and shown that it inhibits host protein synthesis. here, we review the illness that is potentially associated with biological warfare, the pathogen and its deadly molecular mechanism of action, as well as therapeutic developments that may follow.201222817745
case cluster shifting and contaminant source as determinants of melioidosis in taiwan.to assess the geographical distribution of melioidosis contamination sources and the association between the location of melioidosis cases and positive sampling sites for burkholderia pseudomallei in taiwan.201222809327
development of a diagnostic system for burkholderia pseudomallei infections.monoclonal antibodies were generated against whole cell lysate of burkholderia pseudomallei. two out of 6 monoclonal antibodies were found specific and exhibited high affinity against b. pseudomallei, one of which, was utilized to develop sandwich elisa for detection of specific b. pseudomallei antigen. immunoassays were found to be specific as no reaction was observed with closely related burkholderia and pseudomonas species. blood samples from experimentally infected mice were found positive f ...201222806151
the in vivo extracellular life of facultative intracellular bacterial parasites: role in pathogenesis.classically labeled facultative intracellular pathogens are characterized by the ability to have an intracellular phase in the host, which is required for pathogenicity, while capable of extracellular growth in vitro. the ability of these bacteria to replicate in cell-free conditions is usually assessed by culture in artificial bacteriological media. however, the extracellular growth ability of these pathogens may also be expressed by a phase of extracellular infection in the natural setting of ...201322795971
seroepidemiological surveillance of burkholderia pseudomallei in bangladesh.melioidosis (burkholderia pseudomallei infection) has yet to be demonstrated systematically in bangladesh. a prospective, cross-sectional serological survey was conducted in 2010 at six bangladeshi hospitals. age, gender, occupation and residential address were recorded. of 1244 patients, 359 (28.9%) were positive for b. pseudomallei by indirect haemagglutination assay. farmers had an increased risk of seropositivity (risk ratio=1.4, 95% ci 1.0-1.8; p=0.03). there was no clear geographic cluster ...201222795754
imaging spectrum of thoracic melioidosis.melioidosis is predominantly a tropical disease caused by burkholderia pseudomallei, a soil-dwelling gram-negative, aerobic bacillus that is distributed primarily in southeast asia and northern australia. in this pictorial essay, we provide an illustrated review and conceptual framework of the protean imaging features of this infection, along with a brief description of its clinical manifestations and demographic features.201322781630
natural history of inhalation melioidosis in rhesus macaques (macaca mulatta) and african green monkeys (chlorocebus aethiops).burkholderia pseudomallei, the causative agent of melioidosis, is recognized as a serious health threat due to its involvement in septic and pulmonary infections in areas of endemicity and is recognized by the centers for disease control and prevention as a category b biothreat agent. an animal model is desirable to evaluate the pathogenesis of melioidosis and medical countermeasures. a model system that represents human melioidosis infections is essential in this process. a group of 10 rhesus m ...201222778104
role of rela and spot in burkholderia pseudomallei virulence and immunity.burkholderia pseudomallei is a gram-negative soil bacterium and the causative agent of melioidosis, a disease of humans and animals. it is also listed as a category b bioterrorism threat agent by the u.s. centers for disease control and prevention, and there is currently no melioidosis vaccine available. small modified nucleotides such as the hyperphosphorylated guanosine molecules ppgpp and pppgpp play an important role as signaling molecules in prokaryotes. they mediate a global stress respons ...201222778096
malleilactone, a polyketide synthase-derived virulence factor encoded by the cryptic secondary metabolome of burkholderia pseudomallei group pathogens.sequenced bacterial genomes are routinely found to contain gene clusters that are predicted to encode metabolites not seen in fermentation-based studies. pseudomallei group burkholderia are emerging pathogens whose genomes are particularly rich in cryptic natural product biosynthetic gene clusters. we systematically probed the influence of the cryptic secondary metabolome on the virulence of these bacteria and found that disruption of the mal gene cluster, which is natively silent in laboratory ...201222765305
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