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trimethoprim-sulfamethoxazole versus trimethoprim-sulfamethoxazole plus doxycycline as oral eradicative treatment for melioidosis (merth): a multicentre, double-blind, non-inferiority, randomised controlled trial.melioidosis, an infectious disease caused by the gram-negative bacillus burkholderia pseudomallei, is difficult to cure. antimicrobial treatment comprises intravenous drugs for at least 10 days, followed by oral drugs for at least 12 weeks. the standard oral regimen based on trial evidence is trimethoprim-sulfamethoxaxole (tmp-smx) plus doxycycline. this regimen is used in thailand but is associated with side-effects and poor adherence by patients, and tmp-smx alone is recommended in australia. ...201424284287
influence of the molybdenum cofactor biosynthesis on anaerobic respiration, biofilm formation and motility in burkholderia thailandensis.burkholderia thailandensis is closely related to burkholderia pseudomallei, a bacterial pathogen and the causative agent of melioidosis. b. pseudomallei can survive and persist within a hypoxic environment for up to one year and has been shown to grow anaerobically in the presence of nitrate. currently, little is known about the role of anaerobic respiration in pathogenesis of melioidosis. using b. thailandensis as a model, a library of 1344 transposon mutants was created to identify genes requi ...201424239959
pcr-based methodologies used to detect and differentiate the burkholderia pseudomallei complex: b. pseudomallei, b. mallei, and b. thailandensis.methods for the rapid detection and differentiation of the burkholderia pseudomallei complex comprising b. pseudomallei, b. mallei, and b. thailandensis, have been the topic of recent research due to the high degree of phenotypic and genotypic similarities of these species. b. pseudomallei and b. mallei are recognized by the cdc as tier 1 select agents. the high mortality rates of glanders and melioidosis, their potential use as bioweapons, and their low infectious dose, necessitate the need for ...201423969318
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
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
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
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
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
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
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
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
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
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
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
rpos and oxidative stress conditions regulate succinyl-coa: 3-ketoacid-coenzyme a transferase (scot) expression in burkholderia pseudomallei.burkholderia pseudomallei, a pathogenic gram-negative bacterium, causes the severe human disease melioidosis. this organism can survive in eukaryotic host cells by escaping reactive oxygen species via the regulation of stress responsive sigma factors, including rpos. in b. pseudomallei, rpos has been reported to play a role in the oxidative stress response through enhanced activity of oxyr and catalase. in this study, the rpos dependent oxidative stress responsive system was further characterize ...201323808410
environmental management procedures following fatal melioidosis in a captive chimpanzee (pan troglodytes).a 40-yr-old male captive chimpanzee (pan troglodytes) presented with depression and anorexia for 7 days. the tentative diagnosis, following a physical examination under anesthesia, was pneumonia with sepsis. despite antibiotic treatment and supportive care the chimpanzee died a week following presentation. gross pathology confirmed severe purulent pneumonia and diffuse hepatosplenic abscesses. detected in serum at the time of the initial examination, the melioidosis serum antibody titer was elev ...201323805570
antimicrobial action of the cyclic peptide bactenecin on burkholderia pseudomallei correlates with efficient membrane permeabilization.burkholderia pseudomallei is a category b agent that causes melioidosis, an acute and chronic disease with septicemia. the current treatment regimen is a heavy dose of antibiotics such as ceftazidime (caz); however, the risk of a relapse is possible. peptide antibiotics are an alternative to classical antibiotics as they exhibit rapid action and are less likely to result in the development of resistance. the aim of this study was to determine the bactericidal activity against b. pseudomallei and ...201323785532
identification of a predicted trimeric autotransporter adhesin required for biofilm formation of burkholderia pseudomallei.the autotransporters are a large and diverse family of bacterial secreted and outer membrane proteins, which are present in many gram-negative bacterial pathogens and play a role in numerous environmental and virulence-associated interactions. as part of a larger systematic study on the autotransporters of burkholderia pseudomallei, the causative agent of the severe tropical disease melioidosis, we have constructed an insertion mutant in the bpss1439 gene encoding an unstudied predicted trimeric ...201324223950
evaluation of aromatic plants and compounds used to fight multidrug resistant infections.traditional medicine plays a vital role for primary health care in india, where it is widely practiced to treat various ailments. among those obtained from the healers, 78 medicinal plants were scientifically evaluated for antibacterial activity. methanol extract of plants (100  μ g of residue) was tested against the multidrug resistant (mdr) gram-negative and gram-positive bacteria. forty-seven plants showed strong activity against burkholderia pseudomallei (strain tes and khw) and staphylococc ...201324223059
cervical abscesses due to co-infection with burkholderia pseudomallei, salmonella enterica serovar stanley and mycobacterium tuberculosis in a patient with diabetes mellitus.infections due to mycobacterium tuberculosis, burkholderia pseudomallei and non-typhoidal salmonella cause significant morbidity and mortality throughout the world. these intracellular pathogens share some common predisposing factors and clinical features. co-infection with two of these organisms has been reported previously but, to our knowledge, this is the first time that infection with all three has been reported in one person.201324209898
sequence determination of burkholderia pseudomallei strain nctc 13392 colony morphology variants.burkholderia pseudomallei is a biothreat and the causative agent of melioidosis. there are at least seven known colony morphotypes of b. pseudomallei that appear to have different virulence properties in animal models. we report the genome sequence of b. pseudomallei strain nctc 13392 and the genomic variations of its eight morphotype derivatives.201324201202
the in vitro antibiotic susceptibility of malaysian isolates of burkholderia pseudomallei.acute melioidosis may present as localised or septicaemic infections and can be fatal if left untreated. burkholderia pseudomallei resistant to antibiotics used for the treatment of melioidosis had been reported. the aim of this study was to determine the in vitro antibiotic susceptibility patterns of burkholderia pseudomallei isolated in malaysia to a panel of antibiotics used for the treatment of melioidosis and also to potential alternative antibiotics such as tigecycline, ampicillin/sulbacta ...201324194761
sequence-defined transposon mutant library of burkholderia thailandensis.we constructed a near-saturation transposon mutant library for burkholderia thailandensis, a low-virulence surrogate for the causative agent of melioidosis (burkholderia pseudomallei). a primary set of nearly 42,000 unique mutants (~7.5 mutants/gene) was generated using transposon tn5 derivatives. the strains carry insertions in 87% of the predicted protein-coding genes of the organism, corresponding to nearly all of those nonessential for growth on nutrient agar. to achieve high genome coverage ...201324194535
colonial morphotypes and biofilm forming ability of burkholderia pseudomallei.burkholderia pseudomallei the causative agent of melioidosis, is being increasingly recognized as an important cause of morbidity and mortality in south east asia. biofilm formation of b. pseudomallei may be responsible for dormancy, latency and relapse of melioidosis. based on the colonial morphology of the bacteria on b. pseudomallei selective agar medium, seven distinct morphotypes were identified. this study was conducted to assess the in vitro biofilm produced by b. pseudomallei and to inve ...201324189672
correlates of immune protection following cutaneous immunization with an attenuated burkholderia pseudomallei vaccine.infections with the gram-negative bacterium burkholderia pseudomallei (melioidosis) are associated with high mortality, and there is currently no approved vaccine to prevent the development of melioidosis in humans. infected patients also do not develop protective immunity to reinfection, and some individuals will develop chronic, subclinical infections with b. pseudomallei. at present, our understanding of what constitutes effective protective immunity against b. pseudomallei infection remains ...201324101688
the condition-dependent transcriptional landscape of burkholderia pseudomallei.burkholderia pseudomallei (bp), the causative agent of the often-deadly infectious disease melioidosis, contains one of the largest prokaryotic genomes sequenced to date, at 7.2 mb with two large circular chromosomes (1 and 2). to comprehensively delineate the bp transcriptome, we integrated whole-genome tiling array expression data of bp exposed to >80 diverse physical, chemical, and biological conditions. our results provide direct experimental support for the strand-specific expression of 5,4 ...201324068961
a rare cause of septic arthritis: melioidosis.melioidosis is a pyogenic infection with high mortality caused by the bacterium burkholderia pseudomallei. as the clinical presentation is not distinctive, a high index of clinical suspicion is required for diagnosis. we present a case of a 50-year-old farmer who was diabetic and a chronic alcoholic, who presented to us with pneumonia, followed by septic arthritis. he was ultimately diagnosed as having melioidosis.201324067292
less is more: burkholderia pseudomallei and chronic melioidosis.the gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis, a serious infectious disease of humans and animals. once considered an esoteric tropical disease confined to southeast asia and northern australia, research on b. pseudomallei has recently gained global prominence due to its classification as a potential bioterrorism agent by countries such as the united states and also by increasing numbers of case reports from regions where it is not endemic. an enviro ...201324065633
an improved selective culture medium enhances the isolation of burkholderia pseudomallei from contaminated specimens.burkholderia pseudomallei is a gram-negative environmental bacterium found in tropical climates that causes melioidosis. culture remains the diagnostic gold standard, but isolation of b. pseudomallei from heavily contaminated sites, such as fecal specimens, can be difficult. we recently reported that b. pseudomallei is capable of infecting the gastrointestinal tract of mice and suggested that the same may be true in humans. thus, there is a strong need for new culture techniques to allow for eff ...201324062483
prevalence of melioidosis in patients with suspected pulmonary tuberculosis and sputum smear negative for acid-fast bacilli in northeast thailand.the clinical and radiological features of pulmonary melioidosis can mimic tuberculosis. we prospectively evaluated 118 patients with suspected pulmonary tuberculosis who were acid-fast bacilli (afb) smear negative at udon thani hospital, northeast thailand. culture of residual sputum from afb testing was positive for burkholderia pseudomallei in three patients (2.5%; 95% confidence interval [ci] 0.5-7.3%). we propose that in melioidosis-endemic areas, residual sputum from afb testing should be r ...201324062474
spectroscopic and kinetic investigation of the reactions of peroxyacetic acid with burkholderia pseudomallei catalase-peroxidase, katg.catalase-peroxidases or katgs can utilize organic peroxyacids and peroxides instead of hydrogen peroxide to generate the high-valent ferryl-oxo intermediates involved in the catalase and peroxidase reactions. in the absence of peroxidatic one-electron donors, the ferryl intermediates generated with a low excess (10-fold) of peroxyacetic acid (paa) slowly decay to the ferric resting state after several minutes, a reaction that is demonstrated in this work by both stopped-flow uv-vis absorption me ...201324044787
improved diagnosis of melioidosis using a 2-dimensional immunoarray.melioidosis is caused by the gram negative bacterium burkholderia pseudomallei. the gold standard for diagnosis is culture, which requires at least 3-4 days obtaining a result, hindering successful treatment of acute disease. the existing indirect haemagglutination assay (iha) has several disadvantages, in that approximately half of patients later confirmed culture positive are not diagnosed at presentation and a subset of patients are persistently seronegative. we have developed 2 serological a ...201324041552
a case report of melioidosis in a diabetic patient in a union territory.melioidosis is an emerging disease in india. cases have also been reported from south east asia, australia and japan. major risk factors for melioidosis are diabetes mellitus, preexisting renal disease and thalassemia. exposure to contaminated soil and water are also significant occupational hazards associated with the disease. a patient with diabetes of six years duration on regular medication presented with fever, generalised myalgia and headache for a week. blood and bone marrow culture yield ...201324039633
in vitro activities of amoxicillin-clavulanate, doxycycline, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole against biofilm of brazilian strains of burkholderia pseudomallei.this study aimed at investigating the in vitro activities of amoxicillin-clavulanate, doxycycline, ceftazidime, imipenem, and trimethoprim-sulfamethoxazole against burkholderia pseudomallei in planktonic and biofilm forms, through broth microdilution and resazurin-based viability staining, respectively. in planktonic growth, the strains were susceptible to the drugs, while in biofilm growth, significantly higher antimicrobial concentrations were required, especially for ceftazidime and imipenem, ...201324002089
exploiting the burkholderia pseudomallei acute phase antigen bpsl2765 for structure-based epitope discovery/design in structural vaccinology.we solved the crystal structure of burkholderia pseudomallei acute phase antigen bpsl2765 in the context of a structural vaccinology study, in the area of melioidosis vaccine development. based on the structure, we applied a recently developed method for epitope design that combines computational epitope predictions with in vitro mapping experiments and successfully identified a consensus sequence within the antigen that, when engineered as a synthetic peptide, was selectively immunorecognized t ...201323993463
in vitro antimicrobial susceptibility of clinical and environmental strains of burkholderia pseudomallei from brazil. 201323993065
endogenous α2-antiplasmin is protective during severe gram-negative sepsis (melioidosis).α2-antiplasmin (a2ap) is a major inhibitor of fibrinolysis by virtue of its capacity to inhibit plasmin. although the fibrinolytic system is strongly affected by infection, the functional role of a2ap in the host response to sepsis is unknown.201323992406
x-box binding protein 1 (xbp1s) is a critical determinant of pseudomonas aeruginosa homoserine lactone-mediated apoptosis.pseudomonas aeruginosa infections are associated with high mortality rates and occur in diverse conditions including pneumonias, cystic fibrosis and neutropenia. quorum sensing, mediated by small molecules including n-(3-oxo-dodecanoyl) homoserine lactone (c12), regulates p. aeruginosa growth and virulence. in addition, host cell recognition of c12 initiates multiple signalling responses including cell death. to gain insight into mechanisms of c12-mediated cytotoxicity, we studied the role of en ...201323990788
comparative assessment of the intracellular survival of the burkholderia pseudomallei bopc mutant.burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative saprophytic bacterium capable of surviving within phagocytic cells. to assess the role of bopc (a type iii secreted effector protein) in the pathogenesis of b. pseudomallei, a b. pseudomallei bopc mutant was used to infect j774a.1 macrophage-like cells. the bopc mutant showed significantly reduced intracellular survival in infected macrophages compared to wild-type b. pseudomallei. in addition, the bopc mutant disp ...201323990305
burkholderia pseudomallei suppresses caenorhabditis elegans immunity by specific degradation of a gata transcription factor.burkholderia pseudomallei is a gram-negative soil bacterium that infects both humans and animals. although cell culture studies have revealed significant insights into factors contributing to virulence and host defense, the interactions between this pathogen and its intact host remain to be elucidated. to gain insights into the host defense responses to b. pseudomallei infection within an intact host, we analyzed the genome-wide transcriptome of infected caenorhabditis elegans and identified ∼6% ...201323980181
in vitro activity of tebipenem against burkholderia pseudomallei. 201323978354
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
case of paraspinal collection due to burkholderia pseudomallei. 201324132451
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
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