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global analysis of the burkholderia thailandensis quorum sensing-controlled regulon.burkholderia thailandensis contains three acyl-homoserine lactone quorum sensing circuits and has two additional luxr homologs. to identify b. thailandensis quorum sensing-controlled genes, we carried out transcriptome sequencing (rna-seq) analyses of quorum sensing mutants and their parent. the analyses were grounded in the fact that we identified genes coding for factors shown previously to be regulated by quorum sensing among a larger set of quorum-controlled genes. we also found that genes c ...201424464461
melioidosis: molecular aspects of pathogenesis.burkholderia pseudomallei is a gram-negative bacterium that causes melioidosis, a multifaceted disease that is highly endemic in southeast asia and northern australia. this facultative intracellular pathogen possesses a large genome that encodes a wide array of virulence factors that promote survival in vivo by manipulating host cell processes and disarming elements of the host immune system. antigens and systems that play key roles in b. pseudomallei virulence include capsular polysaccharide, l ...201425312349
melioidosis presenting as lymphadenitis: a case report.melioidosis is an infection caused by the facultative intracellular gram-negative bacterium; burkholderia pseudomallei. it gives rise to protean clinical manifestations and has a varied prognosis. although it was rare in sri lanka increasing numbers of cases are being reported with high morbidity and mortality. here we report a case of melioidosis presenting with lymphadenitis which was diagnosed early and treated promptly with a good outcome.201424927768
an improved method for orit-directed cloning and functionalization of large bacterial genomic regions.we have made significant improvements to a broad-host-range system for the cloning and manipulation of large bacterial genomic regions based on site-specific recombination between directly repeated orit sites during conjugation. using two suicide capture vectors carrying flanking homology regions, orit sites are recombined on either side of the target region. using a broad-host-range conjugation helper plasmid, the region between the orit sites is conjugated into an escherichia coli recipient st ...201323747708
melioidosis in traveler from africa to spain.the worldwide epidemiology of melioidosis is changing. we describe a case of acute melioidosis in spain in a patient who had traveled to africa. a novel sequence type of burkholderia pseudomallei was identified in this patient. clinicians should be aware of the possibility of melioidosis in travelers returning from melioidosis-nonendemic regions.201324047798
reliability of automated biochemical identification of burkholderia pseudomallei is regionally dependent.misidentifications of burkholderia pseudomallei as burkholderia cepacia by vitek 2 have occurred. multidimensional scaling ordination of biochemical profiles of 217 malaysian and australian b. pseudomallei isolates found clustering of misidentified b. pseudomallei isolates from malaysian borneo. specificity of b. pseudomallei identification in vitek 2 and potentially other automated identification systems is regionally dependent.201323784129
genomic characterization of jg068, a novel virulent podovirus active against burkholderia cenocepacia.as is true for many other antibiotic-resistant gram-negative pathogens, members of the burkholderia cepacia complex (bcc) are currently being assessed for their susceptibility to phage therapy as an antimicrobial treatment. the objective of this study was to perform genomic and limited functional characterization of the novel bcc phage jg068 (vb_bcep_jg068).201323978260
accurate and rapid identification of the burkholderia pseudomallei near-neighbour, burkholderia ubonensis, using real-time pcr.burkholderia ubonensis is an environmental bacterium belonging to the burkholderia cepacia complex (bcc), a group of genetically related organisms that are associated with opportunistic but generally nonfatal infections in healthy individuals. in contrast, the near-neighbour species burkholderia pseudomallei causes melioidosis, a disease that can be fatal in up to 95% of cases if left untreated. b. ubonensis is frequently misidentified as b. pseudomallei from soil samples using selective culturi ...201323967229
monoclonal antibody-based immunofluorescence microscopy for the rapid identification of burkholderia pseudomallei in clinical specimens.the diagnosis of melioidosis depends on the culture of burkholderia pseudomallei, which takes at least 48 hours. we used a polyclonal-fitc-based immunofluorescence microscopic assay (pab-ifa) on clinical samples to provide a rapid presumptive diagnosis. this has limitations including photobleaching and batch-to-batch variability. this study evaluated an ifa based on a monoclonal antibody specific to b. pseudomallei (mab-ifa) and alexa fluor 488. a diagnostic evaluation was performed on a prospec ...201323716405
antibacterial activity of a lectin-like burkholderia cenocepacia protein.bacteriocins of the llpa family have previously been characterized in the γ-proteobacteria pseudomonas and xanthomonas. these proteins are composed of two mmbl (monocot mannose-binding lectin) domains, a module predominantly and abundantly found in lectins from monocot plants. genes encoding four different types of llpa-like proteins were identified in genomes from strains belonging to the burkholderia cepacia complex (bcc) and the burkholderia pseudomallei group. a selected recombinant llpa-lik ...201323737242
insights into β-lactamases from burkholderia species, two phylogenetically related yet distinct resistance determinants.burkholderia cepacia complex and burkholderia pseudomallei are opportunistic human pathogens. resistance to β-lactams among burkholderia spp. is attributable to expression of β-lactamases (e.g. pena in b. cepacia complex and peni in b. pseudomallei). phylogenetic comparisons reveal that pena and peni are highly related. however, the analyses presented here reveal that pena is an inhibitor-resistant carbapenemase, most similar to kpc-2 (the most clinically significant serine carbapenemase), where ...201323658015
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
in vivo manipulation of γ9(+) t cells in the common marmoset (callithrix jacchus) with phosphoantigen and effect on the progression of respiratory melioidosis.burkholderia pseudomallei is a dangerous human pathogen. phosphoantigens specifically the target primate specific γ9(+)δ2(+) t cells subset and some have been developed as potential immunotherapeutics. previously, we demonstrated that, when stimulated with the phosphoantigen chdmapp, γ9(+)δ2(+) t cells aid in the killing of intracellular b. pseudomallei bacteria. moreover, we found that common marmoset (callithrix jacchus) γ9(+) t cells increase in frequency and respond to the phosphoantigen chd ...201324098670
protection against experimental melioidosis following immunization with live burkholderia thailandensis expressing a manno-heptose capsule.melioidosis is a severe infectious disease caused by burkholderia pseudomallei. it is highly resistant to antibiotic treatment, and there is currently no licensed vaccine. burkholderia thailandensis is a close relative of burkholderia pseudomallei but is essentially avirulent in mammals. in this report, we detail the protective efficacy of immunization with live b. thailandensis e555, a strain which has been shown to express an antigenic capsule similar to that of b. pseudomallei. immunization w ...201323677322
importance of using bruker's security-relevant library for biotyper identification of burkholderia pseudomallei, brucella species, and francisella tularensis. 201323447635
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
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
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
evolutionary analysis of burkholderia pseudomallei identifies putative novel virulence genes, including a microbial regulator of host cell autophagy.burkholderia pseudomallei, the causative agent of melioidosis, contains a large pathogen genome (7.2 mb) with ∼2,000 genes of putative or unknown function. interactions with potential hosts and environmental factors may induce rapid adaptations in these b. pseudomallei genes, which can be discerned through evolutionary analysis of multiple b. pseudomallei genomes. here we show that several previously uncharacterized b. pseudomallei genes bearing genetic signatures of rapid adaptation (positive s ...201324097950
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
polar lipids of burkholderia pseudomallei induce different host immune responses.melioidosis is a disease in tropical and subtropical regions of the world that is caused by burkholderia pseudomallei. in endemic regions the disease occurs primarily in humans and goats. in the present study, we used the goat as a model to dissect the polar lipids of b. pseudomallei to identify lipid molecules that could be used for adjuvants/vaccines or as diagnostic tools. we showed that the lipidome of b. pseudomallei and its fractions contain several polar lipids with the capacity to elicit ...201324260378
a prospective study of the causes of febrile illness requiring hospitalization in children in cambodia.febrile illnesses are pre-eminent contributors to morbidity and mortality among children in south-east asia but the causes are poorly understood. we determined the causes of fever in children hospitalised in siem reap province, cambodia.201323593267
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
functional characterization of burkholderia pseudomallei trimeric autotransporters.burkholderia pseudomallei is a tier 1 select agent and the causative agent of melioidosis, a severe and often fatal disease with symptoms ranging from acute pneumonia and septic shock to a chronic infection characterized by abscess formation in the lungs, liver, and spleen. autotransporters (ats) are exoproteins belonging to the type v secretion system family, with many playing roles in pathogenesis. the genome of b. pseudomallei strain 1026b encodes nine putative trimeric at proteins, of which ...201323716608
melioidosis from contaminated bore water and successful uv sterilization.two cases of melioidosis at a residence in rural northern australia were linked to the unchlorinated domestic bore (automated well) water supply, which was found to have a high concentration of burkholderia pseudomallei. using multilocus sequence typing, clinical b. pseudomallei isolates from both cases were identical to an isolate from the bore water supply. a simple uv sterilizer reduced b. pseudomallei from the domestic water supply to undetectable levels. we have shown that uv treatment is h ...201323751401
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
structural insights into wcbi, a novel polysaccharide-biosynthesis enzyme.capsular polysaccharides (cpss) are protective structures on the surfaces of many gram-negative bacteria. the principal cps of the human pathogen and tier 1 select agent burkholderia pseudomallei consists of a linear repeat of --3)--2-o-acetyl-6-deoxy-β-d-manno-heptopyranose-(1-. this cps is critical to the virulence of this emerging pathogen and represents a key target for the development of novel therapeutics. wcbi is one of several genes in the cps biosynthetic cluster whose deletion leads to ...201325075317
rapid detection of burkholderia pseudomallei in blood cultures using a monoclonal antibody-based immunofluorescent assay.melioidosis is a severe bacterial infection caused by burkholderia pseudomallei. rapid antimicrobial therapy is necessary to improve patient outcome, which is aided by direct detection of b. pseudomallei in clinical samples. a drawback for all antigen assays is that the number of b. pseudomallei in blood usually falls below the achievable level of detection. we performed a prospective cohort study of 461 patients with 541 blood cultures to evaluate the utility of a pre-incubation step prior to d ...201324019434
human melioidosis, malawi, 2011.a case of human melioidosis caused by a novel sequence type of burkholderia pseudomallei occurred in a child in malawi, southern africa. a literature review showed that human cases reported from the continent have been increasing.201323735189
reverse line blot macroarray for simultaneous detection and characterization of four biological warfare agents.the need for a rapid detection and characterization of biowarfare (bw) agents cannot be over emphasized. with diverse array of potential bw pathogen available presently, rapid identification of the pathogen is crucial, so that specific therapy and control measures can be initiated. we have developed a multiplex polymerase chain reaction based reverse line blot macroarray to simultaneously detect four pathogens of bw importance viz. bacillus anthracis, yersinia pestis, brucella melitensis and bur ...201324426077
a sensitive & specific multiplex pcr assay for simultaneous detection of bacillus anthracis, yersinia pestis, burkholderia pseudomallei & brucella species.bacillus anthracis, yersinia pestis, burkholderia pseudomallei and brucella species are potential biowarfare agents. classical bacteriological methods for their identification are cumbersome, time consuming and of potential risk to the handler.201324056564
plant-based hydrocarbon esters from tragia involucrata possess antimicrobial and anti-inflammatory activities.antimicrobial and anti-inflammatory activities of hydrocarbon esters obtained from tragia involucrata were evaluated by disk-diffusion (250 µg/ml), and broth-dilution (500-7.8 µg/ml), methods against bacteria. among the compounds, shellsol showed the most potent activity against burkholderia pseudomallei (khw), aeromonas hydrophila, staphylococcus aureus, bacillus subtilis, streptococcus pyogenes, klebsiella pneumoniae, proteus mirabilis, and streptococcus pneumoniae. interestingly, vinyl hexyle ...201323713670
population-sequencing as a biomarker of burkholderia mallei and burkholderia pseudomallei evolution through microbial forensic analysis.large-scale genomics projects are identifying biomarkers to detect human disease. b. pseudomallei and b. mallei are two closely related select agents that cause melioidosis and glanders. accurate characterization of metagenomic samples is dependent on accurate measurements of genetic variation between isolates with resolution down to strain level. often single biomarker sensitivity is augmented by use of multiple or panels of biomarkers. in parallel with single biomarker validation, advances in ...201324455204
burkholderia mallei and burkholderia pseudomallei cluster 1 type vi secretion system gene expression is negatively regulated by iron and zinc.burkholderia mallei is a facultative intracellular pathogen that causes glanders in humans and animals. previous studies have demonstrated that the cluster 1 type vi secretion system (t6ss-1) expressed by this organism is essential for virulence in hamsters and is positively regulated by the virag two-component system. recently, we have shown that t6ss-1 gene expression is up-regulated following internalization of this pathogen into phagocytic cells and that this system promotes multinucleated g ...201324146925
use of a safe, reproducible, and rapid aerosol delivery method to study infection by burkholderia pseudomallei and burkholderia mallei in mice.burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. burkholderia mallei is a host-adapted clone of b. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in asia, africa, the middle east and south america. infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common ...201324098563
revised structures for the predominant o-polysaccharides expressed by burkholderia pseudomallei and burkholderia mallei.o-polysaccharides (ops) were isolated from purified burkholderia pseudomallei and burkholderia mallei lipopolysaccharides by mild-acid hydrolysis and gel-permeation chromatography. 1-d and 2-d (1)h and (13)c nmr spectroscopy experiments revealed that the ops antigens were unbranched heteropolymers with the following structures: collectively, our results demonstrate that the predominant ops antigens expressed by b. pseudomallei and b. mallei isolates are structurally more complex than previously ...201324056008
animal models for francisella tularensis and burkholderia species: scientific and regulatory gaps toward approval of antibiotics under the fda animal rule.the development and regulatory approval of medical countermeasures (mcms) for the treatment and prevention of bacterial threat agent infections will require the evaluation of products in animal models. to obtain regulatory approval, these models must accurately recapitulate aspects of human disease, including, but not necessarily limited to, route of exposure, time to disease onset, pathology, immune response, and mortality. this article focuses on the state of animal model development for 3 age ...201323628693
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
gas chromatography-mass spectrometry method for rapid identification and differentiation of burkholderia pseudomallei and burkholderia mallei from each other, burkholderia thailandensis and several members of the burkholderia cepacia complex.to develop a simple gas chromatography-mass spectrometry (gc-ms) method for the detection and differentiation of burkholderia pseudomallei and burkholderia mallei from each other, burkholderia thailandensis and several members of the burkholderia cepacia complex.201323879736
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
melioidosis and idiopathic pulmonary hemosiderosis: a cast-iron case.melioidosis is an infection with clinical importance in northern australia due to the high associated mortality despite appropriate therapy. this report presents a case of acute pulmonary melioidosis on a background remarkable for the absence of typical risk factors for infection, but the presence of a high iron pulmonary microenvironment consequent to idiopathic pulmonary hemosiderosis. in light of recent genetic analysis of burkholderia pseudomallei, we postulate that the patient inadvertently ...201325473541
acute pulmonary melioidosis in a child: a case report and review of literature.melioidosis is a rare potentially fatal infection caused by the bacterium burkholderia pseudomallei, which is endemic in southeast asia and northern australia and an emerging pathogen in india. it is a largely under-diagnosed disease and an imitator of tuberculosis, both clinically and radiologically.201324604934
melioidosis :an emerging infection in india.melioidosis caused by the gram-negative bacterium burkholderia pseudomallei is endemic in southeast asia but may be under-diagnosed and under-reported in the indian subcontinent. this study was undertaken to analyse the clinical presentation and epidemiological risk factors for melioidosis in india.201324772696
uncommon clinical presentations of melioidosis in children: 2 cases with sore throat and 1 case with urticarial rash.common clinical presentations of melioidosis in children include suppurative parotitis, lymphadenitis, skin infection and septicemia with pneumonia. here we describe three cases with uncommon presentations of melioidosis seen among children attending a university hospital in northeastern thailand. two patients presented with pharyngitis and subsequently developed cervical lymphadenitis. another patient presented with high fever and generalized urticarial rash. a pharyngeal culture in each of the ...201324437321
osteomyelitis and septic arthritis from infection with burkholderia pseudomallei: a 20-year prospective melioidosis study from northern australia.the gram-negative organism, burkholderia pseudomallei, is responsible for the disease melioidosis. septic arthritis and osteomyelitis due to b. pseudomallei are rare but recognised presentations of the disease.201324403756
case of paraspinal collection due to burkholderia pseudomallei. 201324132451
cytidine derivatives as ispf inhibitors of burkolderia pseudomallei.published biological data suggest that the methyl erythritol phosphate (mep) pathway, a non-mevalonate isoprenoid biosynthetic pathway, is essential for certain bacteria and other infectious disease organisms. one highly conserved enzyme in the mep pathway is 2c-methyl-d-erythritol 2,4-cyclodiphosphate synthase (ispf). fragment-bound complexes of ispf from burkholderia pseudomallei were used to design and synthesize a series of molecules linking the cytidine moiety to different zinc pocket fragm ...201324157367
glyburide reduces bacterial dissemination in a mouse model of melioidosis.burkholderia pseudomallei infection (melioidosis) is an important cause of community-acquired gram-negative sepsis in northeast thailand, where it is associated with a ~40% mortality rate despite antimicrobial chemotherapy. we showed in a previous cohort study that patients taking glyburide ( = glibenclamide) prior to admission have lower mortality and attenuated inflammatory responses compared to patients not taking glyburide. we sought to define the mechanism underlying this observation in a m ...201324147174
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
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
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
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
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
surgical treatment of pseudoaneurysm of innominate artery infected with burkholderia pseudomallei.the management of melioidosis, caused by burkholderia pseudomallei, presenting as an infected pseudoaneurysm requires radical debridement and prolonged antibiotics because the pathogen is resistant to host immunity. an extra-anatomical bypass might be a better treatment choice than in situ graft interposition or other methods.we report on a 76-year-oldman with an infected pseudoaneurysmlocated in the innominate artery and a method of extra-anatomical bypass that has not yet been reported in the ...201327122691
splenic abscess due to chronic melioidosis in a patient previously misdiagnosed as tuberculosis.melioidosis is endemic in southeast asia and northern australia. sporadic cases have been reported from many parts of the world where it has an epidemic potential with high-rate fatality cases. in non-endemic areas, melioidosis may be misdiagnosed with common diseases and this may prove fatal. sporadic cases of melioidosis are mistaken for tuberculosis in india. we report a case of splenic abscess due to chronic melioidosis who was earlier misdiagnosed as tuberculosis and underwent anti-tubercul ...201324714690
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
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
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
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
a melioidosis patient presenting with brainstem signs in the emergency department.neurological abnormalities in melioidosis are rare but may manifest as an acute stroke, and in the emergency department (ed), an inappropriate stroke treatment may threaten a patient's life.201322494598
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
melioidosis in a returning traveller.a 66-year-old man returned to the uk from thailand with a 2-week history of new confusion, hallucinations, fever with rigours and productive cough. he had not responded to (unspecified) antibiotic treatment in thailand. on examination he was afebrile, with an abbreviated mental test score of 8/10 and no other findings on systemic examination. he was treated with ceftriaxone in response to discovery of a gram-negative organism in blood. this was converted to meropenem on the clinical suspicion of ...201323605844
intra-abdominal melioidosis masquerading as a tubercular abdomen: report of a rare case and literature review.melioidosis, caused by burkholderia pseudomallei, an important human pathogen in tropical regions, has protean multi-system clinical manifestations.201323581631
neurologic melioidosis in an imported pigtail macaque (macaca nemestrina).burkholderia pseudomallei is the cause of melioidosis in humans and other animals. disease occurs predominately in asia and australia. it is rare in north america, and affected people and animals typically have a history of travel to (in human cases) or importation from (in animal cases) endemic areas. we describe the gross and histopathologic features and the microbiologic, molecular, and immunohistochemical diagnoses of a case of acute meningoencephalomyelitis and focal pneumonia caused by b. ...201323576240
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
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
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
melioidosis as a consequence of sporting activity.in the tropical city of darwin, northern territory, australia, dry season soil sampling cultured burkholderia pseudomallei from 7 (70%) of 10 sports fields. however, during the 23 years of the darwin prospective melioidosis study, only 5 (0.6%) of 785 melioidosis cases have been attributed to infection from sports fields. in one soccer player with cutaneous melioidosis, b. pseudomallei cultured from the player was identical by multilocus sequence typing and multilocus variable-number tandem repe ...201323732257
melioidosis with a pericardial effusion, which relapsed as a chest wall abscess: a rare presentation.melioidosis, which is caused by a soil saprophyte, burkholderia pseudomallei, is most prevalent in the south-west coast of india. although it is frequently seen in immunocompromised patients, melioidosis can occur in apparently normal individuals. melioidosis can involve almost any organ. a relapse of melioidosis is usually associated with a poor adherence to the eradication therapy, a multifocal involvement and bacteraemia. a relapsing melioidosis is usually known to follow a similar pattern of ...201323730667
melioidosis in an adult male.infection with burkholderia pseudomallei has been described, albeit rarely, patients in bangladesh. infection usually follows percutaneous inoculation or inhalation of the causative bacterium, which is present in soil and surface water in the endemic region. a 35-year-young male farmer presented with prolonged fever and significant weight loss. patient gradually deteriorated despite getting different antibiotics including intravenous ceftriaxone and metronidazole. panels of investigations were d ...201323715373
quorum sensing negatively regulates multinucleate cell formation during intracellular growth of burkholderia pseudomallei in macrophage-like cells.burkholderia pseudomallei is a gram-negative environmental bacterium and the causative agent of melioidosis, a potentially fatal, acute or chronic disease endemic in the tropics. acyl homoserine lactone (ahl)-mediated quorum sensing and signalling have been associated with virulence and biofilm formation in numerous bacterial pathogens. in the canonical acyl-homoserine lactone signalling paradigm, ahls are detected by a response regulator. b. pseudomallei encodes three ahl synthases, encoded by ...201323704903
genome sequence of burkholderia pseudomallei nctc 13392.here, we describe the draft genome sequence of burkholderia pseudomallei nctc 13392. this isolate has been distributed as k96243, but distinct genomic differences have been identified. the genomic sequence of this isolate will provide the genomic context for previously conducted functional studies.201323704173
biogeography of burkholderia pseudomallei in the torres strait islands of northern australia.it has been hypothesized that biogeographical boundaries are a feature of burkholderia pseudomallei ecology, and they impact the epidemiology of melioidosis on a global scale. this study examined the relatedness of b. pseudomallei sourced from islands in the torres strait of northern australia to determine if the geography of isolated island communities is a determinant of the organisms' dispersal. environmental sampling on badu island in the near western island cluster recovered a single clone. ...201323698533
enzymatic and molecular characterisation of leucine aminopeptidase of burkholderia pseudomallei.leucine aminopeptidase (lap) has been known to be a housekeeping protease, dna-binding protein and repressor or activator in the operon regulation of virulence-associated genes in several bacterial species. lap activity was consistently detected in overnight cultures of burkholderia pseudomallei, the causative agent of melioidosis and this enzyme was partially purified and characterised in this study. the intra- and inter-species nucleotide and deduced amino acid sequence variation of lap encodi ...201323682954
environmental factors affecting burkholderia pseudomallei biofilm formation.melioidosis is highly prevalent in northeast thailand which is associated with high incidence of burkholderia pseudomallei present in the soil of this region. b. pseudomallei when present in biofilm becomes resistant to numerous environmental factors and also to certain antibiotics. in this study, we examined the effects of several environmentally relevant factors (salinity, iron, manganese and temperature) on biofilm formation of four clinical ribotypes of b. pseudomallei commonly found in nort ...201323682440
post-exposure therapeutic efficacy of cox-2 inhibition against burkholderia pseudomallei.burkholderia pseudomallei is a gram-negative, facultative intracellular bacillus and the etiologic agent of melioidosis, a severe disease in southeast asia and northern australia. like other multidrug-resistant pathogens, the inherent antibiotic resistance of b. pseudomallei impedes treatment and highlights the need for alternative therapeutic strategies that can circumvent antimicrobial resistance mechanisms. in this work, we demonstrate that host prostaglandin e2 (pge2) production plays a regu ...201323675544
reactive and infective dermatoses associated with adult-onset immunodeficiency due to anti-interferon-gamma autoantibody: sweet's syndrome and beyond.immunodeficiency due to anti-interferon-gamma autoantibody (anti-ifn-γ autoab) is an emerging adult-onset immunodeficiency syndrome predominantly found in southeast asians. it is associated with severe or disseminated infections caused by non-tuberculous mycobacteria (ntm) and other opportunistic pathogens. we describe 3 patients with anti-ifn-γ autoab who developed reactive and infective dermatoses, and thoroughly review the existing literature on dermatoses associated with the immunodeficiency ...201323652167
melioidosis and peritoneal dialysis related peritonitis.we report a case of melioidosis presenting as peritonitis in a patient on continuous ambulatory peritoneal dialysis (capd). a 47-year-old man, a lorry driver, with end-stage renal disease due to diabetes mellitus on capd presented in pd-related peritonitis. he was started on intraperitoneal cloxacillin and ceftazidime, and changed to intraperitoneal vancomycin and meropenam after day 5 due to nonresponse. burkholderia pseudomallei was identified from the dialysate culture. he was treated with in ...201323629573
complete genome sequence of the encephalomyelitic burkholderia pseudomallei strain mshr305.we describe the complete genome sequence of burkholderia pseudomallei mshr305, a clinical isolate taken from a fatal encephalomyelitis case, a rare form of melioidosis. this sequence will be used for comparisons to identify the genes that are involved in neurological cases.201323969058
melioidosis presenting as pseudomyxoma peritonei: yet another pretense of the great mimicker: an unreported entity.melioidosis, a lethal infectious disease caused by burkholderia pseudomallei, an important human pathogen in tropical regions, is notorious for its diverse clinical presentations.201323965152
sinonasal melioidosis in a returned traveller presenting with nasal cellulitis and sinusitis.we illustrate a case involving a 51-year-old man who presented to a tertiary hospital with sepsis secondary to an abscess of the nasal vestibule and pustular eruptions of the nasal mucosa. associated cellulitis extended across the face to the eye, and mucosal thickening of the sinuses was seen on computed tomography. the patient underwent incision and drainage and endoscopic sinus surgery. blood cultures and swabs were positive for a gram-negative bacillus, burkholderia pseudomallei. he had mult ...201323936707
overexpression of activated protein c is detrimental during severe experimental gram-negative sepsis (melioidosis).the interplay between inflammation and blood coagulation is an essential part of host defense during severe pneumosepsis. melioidosis, instigated by the gram-negative bacterium burkholderia pseudomallei, is a frequent cause of pneumosepsis in southeast asia. patients with severe pneumosepsis, including melioidosis, have decreased circulating levels of protein c. activated protein c has anticoagulant and anti-inflammatory properties. in this study, we aimed to investigate the effect of sustained ...201323887233
within-host evolution of burkholderia pseudomallei over a twelve-year chronic carriage infection.burkholderia pseudomallei causes the potentially fatal disease melioidosis. it is generally accepted that b. pseudomallei is a noncommensal bacterium and that any culture-positive clinical specimen denotes disease requiring treatment. over a 23-year study of melioidosis cases in darwin, australia, just one patient from 707 survivors has developed persistent asymptomatic b. pseudomallei carriage. to better understand the mechanisms behind this unique scenario, we performed whole-genome analysis o ...201323860767
sterile-α- and armadillo motif-containing protein inhibits the trif-dependent downregulation of signal regulatory protein α to interfere with intracellular bacterial elimination in burkholderia pseudomallei-infected mouse macrophages.burkholderia pseudomallei, the causative agent of melioidosis, evades macrophage killing by suppressing the trif-dependent pathway, leading to inhibition of inducible nitric oxide synthase (inos) expression. we previously demonstrated that virulent wild-type b. pseudomallei inhibits the trif-dependent pathway by upregulating sterile-α- and armadillo motif-containing protein (sarm) and by inhibiting downregulation of signal regulatory protein α (sirpα); both molecules are negative regulators of t ...201323836818
neurologic melioidosis.melioidosis is an important cause of morbidity and mortality in northern australia and southeast asia. diagnosis is best made by isolation of burkholderia pseudomallei from clinical specimens. a variety of clinical presentations are described, including neurologic disease. the aim of this study was to review admissions with confirmed neurologic melioidosis to a regional hospital in a region to which melioidosis is endemic during 1995-2011. there were 12 culture-confirmed cases of neurologic meli ...201323836574
clinically lesser known entity in india: a report of two cases of melioidosis.melioidosis is endemic in the south asian regions, like thailand, singapore malaysia and australia. the disease is more pronounced in the southern part of the country. it is caused by burkholderia pseudomallei which causes systemic involvement, morbidity and mortality associated with the disease is high. due to highly varied clinical presentation, and low general awareness this infection is largely underdiagnosed and under reported in our country. most laboratories in the country still rely on c ...201323833477
nitro versus hydroxamate in siderophores of pathogenic bacteria: effect of missing hydroxylamine protection in malleobactin biosynthesis. 201323821334
the bpeef-oprc efflux pump is responsible for widespread trimethoprim resistance in clinical and environmental burkholderia pseudomallei isolates.trimethoprim-sulfamethoxazole (co-trimoxazole) is the primary drug used for oral eradication therapy of burkholderia pseudomallei infections (melioidosis). here, we demonstrate that trimethoprim resistance is widespread in clinical and environmental isolates from northeast thailand and northern australia. this resistance was shown to be due to bpeef-oprc efflux pump expression. no dihydrofolate reductase target mutations were involved, although frequent insertion of isbma2 was noted within the p ...201323817379
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