| identification of burkholderia mallei and burkholderia pseudomallei adhesins for human respiratory epithelial cells. | burkholderia pseudomallei and burkholderia mallei cause the diseases melioidosis and glanders, respectively. a well-studied aspect of pathogenesis by these closely-related bacteria is their ability to invade and multiply within eukaryotic cells. in contrast, the means by which b. pseudomallei and b. mallei adhere to cells are poorly defined. the purpose of this study was to identify adherence factors expressed by these organisms. | 2010 | 20920184 |
| unraveling type iii secretion systems in the highly versatile burkholderia pseudomallei. | burkholderia pseudomallei is a highly versatile pathogen capable of infecting many species of animals and plants. it is the causative agent of melioidosis, a medically important infectious disease in humans with a wide spectrum of disease manifestations. its versatility as a pathogen is reflected in its huge 7.2mb genome and the many virulence mechanisms it possesses, including three different type iii secretion systems (t3sss). recent elucidation of the regulatory network of t3ss3 and the chara ... | 2010 | 20951592 |
| melioidosis in malaysia. | melioidosis is an important cause of sepsis in the tropics, is caused by an environmental saprophyte--b. pseudomallei. it affects mainly adults with underlying predisposing condition such as diabetes. the range of symptoms varies from benign and localized abscesses, to severe community-acquired pneumonia to acute fulminating septicaemia with multiple abscesses often leading to death. b. pseudomallei is an intracellular pathogen and some of the virulence mechanisms that govern the complex interac ... | 2009 | 20954549 |
| incidence, risk factors and clinical epidemiology of melioidosis: a complex socio-ecological emerging infectious disease in the alor setar region of kedah, malaysia. | melioidosis, a severe and fatal infectious disease caused by burkholderia pseudomallei, is believed to an emerging global threat. however, data on the natural history, risk factors, and geographic epidemiology of the disease are still limited. | 2010 | 20964837 |
| in vitro activity of cethromycin against burkholderia pseudomallei and investigation of mechanism of resistance. | most burkholderia pseudomallei strains are intrinsically resistant to macrolides, mainly due to amrab-opra- and/or bpeab-oprb-mediated efflux. we assessed the in vitro anti-b. pseudomallei efficacy of cethromycin, a novel ketolide with broad-spectrum activity against gram-negative and gram-positive pathogens. | 2010 | 20965890 |
| [the clinical manifestations of three cases with melioidosis]. | to investigate the clinical features of 3 cases of burkholderia pseudomallei septicemia in guangxi province, and therefore to improve its diagnosis and treatment. | 2010 | 20979813 |
| resolvase-like serine recombinase mediates integration/excision in the bacteriophage φrsm. | ϕrsm1, a filamentous phage infecting ralstonia solanacearum, encodes an open reading frame (orf14) that exhibits significant homology to members of the resolvase/invertase subfamily of site-specific serine recombinases. similar prophages are found in the genomes of various strains of r. solanacearum, r. pickettii, and burkholderia pseudomallei. we have characterized the integrative and excisive recombination reactions mediated by the ϕrsm1 integrase using in vivo assays. an e. coli plasmid conta ... | 2010 | 21035394 |
| pathogenicity of high-dose enteral inoculation of burkholderia pseudomallei to mice. | melioidosis is a frequently lethal tropical infection caused by the environmental saprophyte burkholderia pseudomallei. although transcutaneous inoculation and inhalation are considered the primary routes of infection, suggestive clinical evidence implicates ingestion as a possible alternative route. we show that in balb/c and c57bl/6 mice, direct gastric inoculation of high doses of b. pseudomallei causes systemic infection that may be lethal or cause chronic disseminated infection. mice may sh ... | 2010 | 21036839 |
| burkholderia pseudomallei proteins presented by monocyte-derived dendritic cells stimulate human memory t cells in vitro. | melioidosis is a severe infectious disease caused by the saprophytic facultative intracellular pathogen burkholderia pseudomallei. the disease is endemic in southeast asia and northern australia, and no effective vaccine exists. to describe human cell-mediated immune responses to b. pseudomallei and to identify candidate antigens for vaccine development, the ability of antigen-pulsed monocyte-derived dendritic cells (modcs) to trigger autologous t-cell responses to b. pseudomallei and its produc ... | 2010 | 21041491 |
| cerebral abscess and calvarial osteomyelitis due to burkholderia pseudomallei. | | 2010 | 21045524 |
| systemic melioidosis presenting as suppurative parotitis. | a 3 year old child was brought with fever, left parotid swelling and altered sensorium. cultures from blood, pus and throat swab grew burkholderia pseudomallei. a diagnosis of septicemic melioidosis with encephalopathy was made. she recovered following treatment with parenteral ceftazidime for 14 days, and 6 months of oral co trimoxazole and amoxycillin clavulanate. she is doing well on follow-up. | 2010 | 21048270 |
| role of burkholderia pseudomallei in the invasion, replication and induction of apoptosis in human epithelial cell lines. | burkholderia pseudomallei is a bacterial pathogen causing melioidosis. in the present study, we demonstrated the effects of b. pseudomallei capsular polysaccharide on the invasion, intracellular replication, induction of cytotoxicity and apoptosis of human epithelial hela and a549 cells. the b. pseudomallei capsule mutant had a significantly greater ability to invade both cell lines (p < 0.05). the b. pseudomallei capsule mutant had a greater ability to induce apoptosis in a549 cells than wild t ... | 2010 | 21073038 |
| antibiosis of burkholderia ubonensis againist burkholderia pseudomallei, the causative agent for melioidosis. | melioidosis, caused by burkholderia pseudomallei, is an enigmatic infectious disease that afflicts individuals in many tropical and developing regions. treatment is hampered by the organism's innate antibiotic resistance and the disease's non-pathognomic presentation. recently, added attention has been given to this organism due to its classification as a potential biowarfare agent. therefore, methods of preventing acquisition of infection are needed. we investigated antagonism between burkholde ... | 2010 | 21073065 |
| randomized soil survey of the distribution of burkholderia pseudomallei in rice fields in laos. | melioidosis is a major cause of morbidity and mortality in southeast asia, where the causative organism (burkholderia pseudomallei) is present in the soil. in the lao people's democratic republic (laos), b. pseudomallei is a significant cause of sepsis around the capital, vientiane, and has been isolated in soil near the city, adjacent to the mekong river. we explored whether b. pseudomallei occurs in lao soil distant from the mekong river, drawing three axes across northwest, northeast, and sou ... | 2010 | 21075883 |
| molecular analysis of antimicrobial agent translocation through the membrane porin bpsomp38 from an ultraresistant burkholderia pseudomallei strain. | burkholderia pseudomallei (bps) is a gram-negative bacterium that causes melioidosis, an infectious disease of animals and humans common in northern and north-eastern parts of thailand. successful treatment of melioidosis is difficult due to intrinsic resistance of bps to various antibacterial agents. it has been suggested that the antimicrobial resistance of this organism may result from poor permeability of the active compounds through porin channels located in the outer membrane (om) of the b ... | 2010 | 21078354 |
| size distribution and buoyant density of burkholderia pseudomallei. | the size and density of microbial cells determine the time that pathogens can remain airborne and thus, their potential to infect by the respiratory route. we determined the density and size distribution of burkholderia pseudomallei cells in comparison with other burkholderia species, including b. mallei and b. thailandensis, all prepared and analyzed under similar conditions. the observed size distribution and densities of several bacterial strains indicates that aerosolized particles consistin ... | 2010 | 21080156 |
| nucleotide-binding oligomerization domain-containing protein 2 regulates suppressor of cytokine signaling 3 expression in burkholderia pseudomallei- infected mouse macrophage cell line raw 264.7. | burkholderia pseudomallei, a causative agent of melioidosis, is a facultative intracellular gram-negative bacterium that can survive and multiply inside the macrophages. toll-like receptors are one class of pattern recognition receptors (prrs) that have been documented to play significant role in b. pseudomallei infection. in the present study, we investigated a potential role of nucleotide-binding oligomerization domain-containing protein 1 and 2 (nod1 and nod2), cytoplasmic pattern recognition ... | 2010 | 21088051 |
| novel lytic bacteriophages from soil that lyse burkholderia pseudomallei. | burkholderia pseudomallei is a gram-negative saprophytic bacterium that causes severe sepsis with a high mortality rate in humans and a vaccine is not available. bacteriophages are viruses of bacteria that are ubiquitous in nature. several lysogenic phages of burkholderia spp. have been found but information is scarce for lytic phages. six phages, st2, st7, st70, st79, st88 and st96, which lyse b. pseudomallei, were isolated from soil in an endemic area. the phages belong to the myoviridae famil ... | 2010 | 21091532 |
| burkdiff: a real-time pcr allelic discrimination assay for burkholderia pseudomallei and b. mallei. | a real-time pcr assay, burkdiff, was designed to target a unique conserved region in the b. pseudomallei and b. mallei genomes containing a snp that differentiates the two species. sensitivity and specificity were assessed by screening burkdiff across 469 isolates of b. pseudomallei, 49 isolates of b. mallei, and 390 isolates of clinically relevant non-target species. concordance of results with traditional speciation methods and no cross-reactivity to non-target species show burkdiff is a robus ... | 2010 | 21103048 |
| genome wide transcriptome profiling of a murine acute melioidosis model reveals new insights into how burkholderia pseudomallei overcomes host innate immunity. | at present, very little is known about how burkholderia pseudomallei (b. pseudomallei) interacts with its host to elicit melioidosis symptoms. we established a murine acute-phase melioidosis model and used dna microarray technology to investigate the global host/pathogen interaction. we compared the transcriptome of infected liver and spleen with uninfected tissues over an infection period of 42 hr to identify genes whose expression is altered in response to an acute infection. | 2010 | 21110886 |
| effect of colony morphology variation of burkholderia pseudomallei on intracellular survival and resistance to antimicrobial environments in human macrophages in vitro. | primary diagnostic cultures from patients with melioidosis demonstrate variation in colony morphology of the causative organism, burkholderia pseudomallei. variable morphology is associated with changes in the expression of a range of putative virulence factors. this study investigated the effect of b. pseudomallei colony variation on survival in the human macrophage cell line u937 and under laboratory conditions simulating conditions within the macrophage milieu. isogenic colony morphology type ... | 2010 | 21114871 |
| a conference report from "down under": talking autophagy at ozbio2010. | ozbio2010 was held at the melbourne convention and exhibition centre, september 26 to october 1, 2010. this international conference catered to researchers in several fields having complementary interests including biochemistry, molecular biology, cell biology, plant physiology and health-related research. it was held under the auspices of two major international scientific societies, iubmb and faobmb, and the combio2010 collective (representing nine professional societies and groupings from aus ... | 2011 | 21116128 |
| the epidemiology and clinical spectrum of melioidosis: 540 cases from the 20 year darwin prospective study. | over 20 years, from october 1989, the darwin prospective melioidosis study has documented 540 cases from tropical australia, providing new insights into epidemiology and the clinical spectrum. | 2010 | 21152057 |
| identification of immunoreactive secretory proteins from the stationary phase culture of burkholderia pseudomallei. | bacterial secreted proteins are known to be involved in virulence and may mediate important host-pathogen interactions. in this study, when the stationary phase culture supernatant of burkholderia pseudomallei was subjected to 2-de, 113 protein spots were detected. fifty-four of the secreted proteins, which included metabolic enzymes, transcription/translation regulators, potential virulence factors, chaperones, transport regulators, and hypothetical proteins, were identified using ms and databa ... | 2010 | 21170972 |
| construction and molecular characterization of mouse single-chain variable fragment antibodies against burkholderia mallei and burkholderia pseudomallei. | we have selected two lipopolysaccharide (lps) specific burkholderia mallei mouse monoclonal antibodies (mabs) and four anti-capsular b. pseudomallei-specific mabs to generate mouse single-chain variable fragment (scfv) antibodies. this selection was made through extensive in vitro and in vivo assay from our library of mabs against b. mallei and b. pseudomallei. we initially generated the mouse immunoglobulin variable heavy chain (vh) and light chain (vl) regions from each of these six selected m ... | 2010 | 21172353 |
| novel pan-genomic analysis approach in target selection for multiplex pcr identification and detection of burkholderia pseudomallei, burkholderia thailandensis, and burkholderia cepacia complex species: a proof-of-concept study. | burkholderia pseudomallei, burkholderia thailandensis, and the burkholderia cepacia complex differ greatly in pathogenicity and epidemiology. yet, they are occasionally misidentified by biochemical profiling, and even 16s rrna gene sequencing may not offer adequate discrimination between certain species groups. using the 23 b. pseudomallei, four b. thailandensis, and 16 b. cepacia complex genome sequences available, we identified gene targets specific to each of them (a tat domain protein, a 70- ... | 2010 | 21177905 |
| immunospecific responses to bacterial elongation factor tu during burkholderia infection and immunization. | burkholderia pseudomallei is the etiological agent of melioidosis, a disease endemic in parts of southeast asia and northern australia. currently there is no licensed vaccine against infection with this biological threat agent. in this study, we employed an immunoproteomic approach and identified bacterial elongation factor-tu (ef-tu) as a potential vaccine antigen. ef-tu is membrane-associated, secreted in outer membrane vesicles (omvs), and immunogenic during burkholderia infection in the muri ... | 2010 | 21179405 |
| cd4+ t-cell immunity to the burkholderia pseudomallei abc transporter lolc in melioidosis. | burkholderia pseudomallei causes melioidosis, a disease with a wide range of possible outcomes, from seroconversion and dormancy to sepsis and death. this spectrum of host-pathogen interactions poses challenging questions about the heterogeneity in immunity to b. pseudomallei. models show protection to be dependent on cd4(+) cells and ifn-γ, but little is known about specific target antigens. having previously implicated the abc transporter, lolc, in protective immunity, we here use epitope pred ... | 2010 | 21182082 |
| autophagy targeting of listeria monocytogenes and the bacterial countermeasure. | autophagy acts as an intrinsic defense system against intracellular bacterial survival. recently, multiple cellular pathways that target intracellular bacterial pathogens to autophagy have been described. these include the atg5/lc3 pathway, which targets shigella, the ubiquitin (ub)-ndp52-lc3 pathway, which targets group a streptococcus (gas) and salmonella typhimurium, the ub-p62-lc3 pathway, which targets mycobacterium tuberculosis, listeria monocytogenes and s. typhimurium, and the diacylglyc ... | 2011 | 21193840 |
| melioidosis presenting as sepsis syndrome: a case report. | melioidosis is an important disease in asia and australia. it is very rare in venezuela. we describe the case of a 50-year-old diabetic patient with several episodes of right tibial osteomyelitis, left shoulder arthritis, sternal osteomyelitis, right parietal osteomyelitis, and subperiosteal abscess, followed by septic arthritis of the right knee. in all cases gram stain smear showed gram-negative bacilli. culture yielded burkholderia pseudomallei, susceptible to third- and fourth-generation cep ... | 2010 | 21195650 |
| genome-wide analysis reveals loci encoding anti-macrophage factors in the human pathogen burkholderia pseudomallei k96243. | burkholderia pseudomallei is an important human pathogen whose infection biology is still poorly understood. the bacterium is endemic to tropical regions, including south east asia and northern australia, where it causes melioidosis, a serious disease associated with both high mortality and antibiotic resistance. b. pseudomallei is a gram-negative facultative intracellular pathogen that is able to replicate in macrophages. however despite the critical nature of its interaction with macrophages, ... | 2010 | 21203527 |
| impact of streptozotocin-induced diabetes on functional responses of dendritic cells and macrophages towards burkholderia pseudomallei. | diabetes mellitus is a documented risk factor for melioidosis, a tropical infection caused by burkholderia pseudomallei. the increased susceptibility of diabetic individuals to infections with other pathogens has been associated with immune dysregulation. however, the impact of diabetes on the functional responses of dendritic cells (dc) and macrophages during b. pseudomallei infection has not been investigated. this study compared the responses of macrophages and dc towards b. pseudomallei usin ... | 2011 | 21204999 |
| fatal acute melioidosis in a tourist returning from martinique island, november 2010. | we report the fatal case of acute melioidosis in a patient returning from martinique with fever in november 2010. gram-negative rods were isolated from a blood culture and burkholderia pseudomallei identified within 24 hours after first medical contact. the patient died two days after admission to hospital despite intravenous therapy with high doses of imipenem/cilastatin and intensive care. clinicians seeing travellers returning from the subtropics or tropics with severe pneumonia or septicaemi ... | 2011 | 21223835 |
| macrophage and galleria mellonella infection models reflect the virulence of naturally occurring isolates of b. pseudomallei, b. thailandensis and b. oklahomensis. | burkholderia pseudomallei is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. in murine models of infection, different strains exhibit varying degrees of virulence. in contrast, two related species, b. thailandensis and b. oklahomensis, are highly attenuated in mice. our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (galleria mellonella) infection models. | 2011 | 21241461 |
| burkavidin: a novel secreted biotin-binding protein from the human pathogen burkholderia pseudomallei. | the avidin-biotin technology has many applications, including molecular detection; immobilization; protein purification; construction of supramolecular assemblies and artificial metalloenzymes. here we present the recombinant expression of novel biotin-binding proteins from bacteria and the purification and characterization of a secreted burkavidin from the human pathogen burkholderia pseudomallei. expression of the native burkavidin in escherichia coli led to periplasmic secretion and formation ... | 2011 | 21241807 |
| metabolites from the induced expression of cryptic single operons found in the genome of burkholderia pseudomallei. | bacterial genome sequencing projects routinely uncover gene clusters that are predicted to encode the biosynthesis of uncharacterized small molecules. a subset of these cryptic genetic elements appears as individual operons. here we investigate potential single-operon biosynthetic systems found in the genome of the pathogenic bacterium burkholderia pseudomallei . placing these operons under the control of an inducible promoter led to the production of seven new metabolites. among the molecules w ... | 2011 | 21247113 |
| n-octanoylhomoserine lactone signalling mediated by the bpsi-bpsr quorum sensing system plays a major role in biofilm formation of burkholderia pseudomallei. | the genome of burkholderia pseudomallei encodes three acylhomoserine lactone (ahl) quorum sensing systems, each comprising an ahl synthase and a signal receptor/regulator. the bpsi-bpsr system produces n-octanoylhomoserine lactone (c8hl) and is positively auto-regulated by its ahl product. the products of the remaining two systems have not been identified. in this study, tandem ms was used to identify and quantify the ahl species produced by three clinical b. pseudomallei isolates - khw, k96243 ... | 2011 | 21252275 |
| identification of immunoreactive secretory proteins from the stationary phase culture of burkholderia pseudomallei. | bacterial secreted proteins are known to be involved in virulence and may mediate important host-pathogen interactions. in this study, when the stationary phase culture supernatant of burkholderia pseudomallei was subjected to 2-de, 113 protein spots were detected. fifty-four of the secreted proteins, which included metabolic enzymes, transcription/translation regulators, potential virulence factors, chaperones, transport regulators, and hypothetical proteins, were identified using ms and databa ... | 2010 | 21254130 |
| development of ceftazidime resistance in burkhoderia pseudomallei in a patient experiencing melioidosis with mediastinal lymphadenitis. | | 2010 | 21274496 |
| burkholderia pseudomallei antibodies in individuals living in endemic regions in northeastern brazil. | a seroepidemiological investigation was conducted among the population of two municipalities in northeastern brazil. immunoglobulin m (igm) and igg antibodies to burkholderia pseudomallei were positive in 51.27% (161 in 317 samples) and 58.49% (186), respectively. igm titers were higher in children than in adults. on the contrary, igg increased progressively with age. we observed a significant association between agricultural occupation and raised igm titers (p < 0.005) and igg titers (p < 0.001 ... | 2011 | 21292903 |
| glyburide is anti-inflammatory and associated with reduced mortality in melioidosis. | patients with diabetes mellitus are more prone to bacterial sepsis, but there are conflicting data on whether outcomes are worse in diabetics after presentation with sepsis. glyburide is an oral hypoglycemic agent used to treat diabetes mellitus. this k(atp)-channel blocker and broad-spectrum atp-binding cassette (abc) transporter inhibitor has broad-ranging effects on the immune system, including inhibition of inflammasome assembly and would be predicted to influence the host response to infect ... | 2011 | 21293047 |
| [a case of melioidosis in argentina]. | we describe a case of 17-year- old man native of dominican republic, with hodgkin's lymphoma, who presented soft espontaneous draining nodules. in the clinical samples grew burkholderia pseudomallei; the etiological agent of melioidosis. he received antimicrobial treatment with imipenem and amoxicillin/clavulanic with very good clinical evolution of the infectious process. melioidosis diagnosis could be underestimated due to the low incidence of burkholderia pseudomallei in our continent. the de ... | 2011 | 21296719 |
| five-year surveillance for burkholderia pseudomallei in thailand from 2000 to 2004: prevalence and antimicrobial susceptibility. | to determine the prevalence and antibiotic susceptibility patterns of burkholderia pseudomallei isolates in thailand from 2000 to 2004. | 2009 | 21298845 |
| an overview of antimicrobial susceptibility patterns for gram-negative bacteria from the national antimicrobial resistance surveillance thailand (narst) program from 2000 to 2005. | the national antimicrobial resistance surveillance thailand (narst) has been initiated since 1998 to strengthen the surveillance program for antimicrobial-resistant pathogens as well as to standardize the laboratory practices in thailand. this collaborative network was funded by the world health organization, and involved 33 hospitals throughout thailand at the first phase. nevertheless, no prior effort has been made to share the antimicrobial resistance data in the national level. in this overv ... | 2009 | 21298849 |
| renal allograft recipient with melioidosis of the urinary tract. | | 2011 | 21299774 |
| human immune responses to burkholderia pseudomallei characterized by protein microarray analysis. | we aimed to determine the antibody and t cell responses to burkholderia pseudomallei of humans to select candidate vaccine antigens. | 2011 | 21300673 |
| the cluster 1 type vi secretion system is a major virulence determinant in burkholderia pseudomallei. | the burkholderia pseudomallei k96243 genome encodes six type vi secretion systems (t6sss), but little is known about the role of these systems in the biology of b. pseudomallei. in this study, we purified recombinant hcp proteins from each t6ss and tested them as vaccine candidates in the balb/c mouse model of melioidosis. recombinant hcp2 protected 80% of mice against a lethal challenge with k96243, while recombinant hcp1, hcp3, and hcp6 protected 50% of mice against challenge. hcp6 was the onl ... | 2011 | 21300775 |
| dna fingerprinting of septicemic and localized burkholderia pseudomallei isolates from malaysian patients. | we have analysed dna fingerprinting patterns by pulsed-field gel electrophoresis (pfge) of 52 unrelated burkholderia pseudomallei strains isolated from septicemic and localized infections from malaysian subjects. a total of 38 pfge types were observed among 36 septicemic and 16 localized strains with no predominant pattern. type 25 was seen in 2 epidemiologically related strains, suggesting human to human transmission. twelve pfge types were shared among 26 strains (21 septicemic and 5 localized ... | 2011 | 21323173 |
| receptor mimicry as novel therapeutic treatment for biothreat agents. | the specter of intentional release of pathogenic microbes and their toxins is a real threat. this article reviews the literature on adhesins of biothreat agents, their interactions with oligosaccharides and the potential for anti-adhesion compounds as an alternative to conventional therapeutics. the minimal binding structure of ricin has been well characterised and offers the best candidate for successful anti-adhesion therapy based on the galβ1-4glcnac structure. the botulinum toxin serotypes a ... | 2010 | 21327124 |
| identification of motifs of burkholderia pseudomallei bima required for intracellular motility, actin binding, and actin polymerization. | actin-based motility of the melioidosis pathogen burkholderia pseudomallei requires bima (burkholderia intracellular motility a). the mechanism by which bima mediates actin assembly at the bacterial pole is ill-defined. toward an understanding of the regions of b. pseudomallei bima required for intracellular motility and the binding and polymerization of actin, we constructed plasmid-borne bima variants and glutathione-s-transferase fusion proteins with in-frame deletions of specific motifs. a 1 ... | 2011 | 21335455 |
| elucidation of the regulon and cis-acting regulatory element of hrpb, the arac-type regulator of a plant pathogen-like type iii secretion system in burkholderia pseudomallei. | the human pathogen burkholderia pseudomallei possesses multiple type iii secretion system (t3ss) gene clusters. one of these, the b. pseudomallei t3ss2 (t3ss2(bp)) gene cluster, which apparently plays no role in animal virulence, is also found in six additional burkholderia spp. and is very similar to t3sss found in phytopathogenic xanthomonas spp. and ralstonia solanacearum. the t3ss2(bp) gene cluster also encodes an arac-type regulatory protein (hrpb(bp)) that is an ortholog of hrpb, the maste ... | 2011 | 21335458 |
| leveraging structure determination with fragment screening for infectious disease drug targets: mecp synthase from burkholderia pseudomallei. | as part of the seattle structural genomics center for infectious disease, we seek to enhance structural genomics with ligand-bound structure data which can serve as a blueprint for structure-based drug design. we have adapted fragment-based screening methods to our structural genomics pipeline to generate multiple ligand-bound structures of high priority drug targets from pathogenic organisms. in this study, we report fragment screening methods and structure determination results for 2c-methyl-d ... | 2011 | 21359640 |
| predicting the success of fragment screening by x-ray crystallography. | fragment screening using x-ray crystallography is a method that can provide direct three-dimensional readouts of the structures of protein-small molecule complexes for lead development and fragment-based drug discovery. with current technology, an amenable crystal form can be screened crystallographically against a library of 1000-2000 fragments in 1-2 weeks. we have performed over a dozen crystallographic screening campaigns using our own compound collection called fragments of life™ (fol). whi ... | 2011 | 21371588 |
| systemic melioidiosis. | | 2011 | 21378433 |
| outer membrane proteome of burkholderia pseudomallei and burkholderia mallei from diverse growth conditions. | burkholderia mallei and burkholderia pseudomallei are closely related, aerosol-infective human pathogens that cause life-threatening diseases. biochemical analyses requiring large-scale growth and manipulation at biosafety level 3 under select agent regulations are cumbersome and hazardous. we developed a simple, safe, and rapid method to prepare highly purified outer membrane (om) fragments from these pathogens. shotgun proteomic analyses of oms by trypsin shaving and mass spectrometry identifi ... | 2011 | 21391724 |
| mechanism and inhibition of the fabi enoyl-acp reductase from burkholderia pseudomallei. | as an initial step in developing novel antibacterials against burkholderia pseudomallei, we have characterized the fabi enoyl-acp reductase homologues in the type ii fatty acid biosynthesis pathway from this organism and performed an initial enzyme inhibition study. | 2011 | 21393229 |
| dna fingerprinting of human isolates of burkholderia pseudomallei from different geographical regions of malaysia. | melioidosis is an infectious disease caused by burkholderia pseudomallei and endemic in southeast asia. one hundred and forty six clinical isolates of b. pseudomallei from different states in malaysia were obtained and molecular typing was carried out using pulsed-field gel electrophoresis (pfge). overall, nine clusters were successfully identified. burkholderia pseudomallei isolates used in this study were found to be genetically diverse and there were differences in the clusters of isolates fr ... | 2010 | 21399594 |
| dictyostelium discoideum as a model system for identification of burkholderia pseudomallei virulence factors. | burkholderia pseudomallei is an emerging bacterial pathogen and category b biothreat. human infections with b. pseudomallei (called melioidosis) present as a range of manifestations, including acute septicemia and pneumonia. although melioidosis can be fatal, little is known about the molecular basis of b. pseudomallei pathogenicity, in part because of the lack of simple, genetically tractable eukaryotic models to facilitate en masse identification of virulence determinants or explore host-patho ... | 2011 | 21402765 |
| complete killing of caenorhabditis elegans by burkholderia pseudomallei is dependent on prolonged direct association with the viable pathogen. | burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. much remains to be known about the contributions of genotypic variations within the bacteria and the host, and environmental factors that lead to the manifestation of the clinical symptoms of melioidosis. | 2011 | 21408228 |
| distinct roles for nitric oxide in resistant c57bl/6 and susceptible balb/c mice to control burkholderia pseudomallei infection. | burkholderia pseudomallei is the causative agent of melioidosis, an emerging bacterial infectious disease in tropical and subtropical areas. we recently showed that nadph oxidase but not nitric oxide (no) contributes to resistance in innately resistant c57bl/6 mice in a b. pseudomallei respiratory infection model. however, the function of no for resistance was shown to differ among distinct strains of mice and proved also to be stage dependent in various infection models. the present study there ... | 2011 | 21410970 |
| the burkholderia pseudomallei type iii secretion system and bopa are required for evasion of lc3-associated phagocytosis. | burkholderia pseudomallei is the causative agent of melioidosis, a fatal infectious disease endemic in tropical regions worldwide, and especially prevalent in southeast asia and northern australia. this intracellular pathogen can escape from phagosomes into the host cytoplasm, where it replicates and infects adjacent cells. we previously demonstrated that, in response to b. pseudomallei infection of macrophage cell line raw 264.7, a subset of bacteria co-localized with the autophagy marker prote ... | 2011 | 21412437 |
| development of reagents and assays for the detection of pathogenic burkholderia species. | rapid detection of the category b biothreat agents burkholderia pseudomallei and burkholderia mallei in acute infections is critical to ensure that appropriate treatment is administered quickly to reduce an otherwise high probability of mortality (ca. 40% for b. pseudomallei). we are developing assays that can be used in clinical laboratories or security applications for the direct detection of surface-localized and secreted macromolecules produced by these organisms. we present our current medi ... | 2011 | 21413172 |
| vith world melioidosis congress report: celebrating a century of research. | | 2011 | 21449838 |
| in vitro and in vivo studies of monoclonal antibodies with prominent bactericidal activity against burkholderia pseudomallei and burkholderia mallei. | our laboratory has developed more than a hundred mouse monoclonal antibodies (mabs) against burkholderia pseudomallei and burkholderia mallei. these antibodies have been categorized into different groups based on their specificities and the biochemical natures of their target antigens. the current study first examined the bactericidal activities of a number of these mabs by an in vitro opsonic assay. then, the in vivo protective efficacy of selected mabs was evaluated using balb/c mice challenge ... | 2011 | 21450976 |
| comparative in vitro susceptibility of burkholderia pseudomallei to doripenem, ertapenem, tigecycline and moxifloxacin. | burkholderia pseudomallei, the causative agent of melioidosis, continues to present therapeutic challenges in endemic areas. a number of clinical issues have prompted consideration of alternative antimicrobial therapies. these include stability in 24-h infusion pumps, broad-spectrum coverage in the empirical treatment of community-acquired pneumonia, cost, the need for effective oral agents and rare reports of emerging resistance. this study aimed to examine the in vitro susceptibility of b. pse ... | 2011 | 21481571 |
| molecular phylogeny of burkholderia pseudomallei from a remote region of papua new guinea. | the island of new guinea is located midway between the world's two major melioidosis endemic regions of australia and southeast asia. previous studies in papua new guinea have demonstrated autochthonous melioidosis in balimo, western province. in contrast to other regions of endemicity, isolates recovered from both environmental and clinical sources demonstrate narrow genetic diversity over large spatial and temporal scales. | 2011 | 21483841 |
| mycotic aneurysm caused by burkholderia pseudomallei: report of a brazilian strain genetically related to thai strains. | clin microbiol infect 2011; 17: 719-721 abstract: melioidosis, a severe infectious disease caused by burkholderia pseudomallei that is prevalent in southeast asia and northern australia, has been sporadically reported in brazil since 2003. we report a case of aortic aneurysm with blood culture positive for b. pseudomallei. the phylogenetic analysis of 16s ribosomal dna showed this isolate to be evolutionarily grouped with the mshr346 strains from thailand. | 2011 | 21521412 |
| adaptation and antibiotic tolerance of anaerobic burkholderia pseudomallei. | the gram-negative bacterium, burkholderia pseudomallei, is the etiological agent of melioidosis and is remarkably resistant to most classes of antibacterials. even after months of treatment with antibacterials relatively effective in vitro, there is a high rate of treatment failure, indicating that this pathogen alters its patterns of antibacterial susceptibility in response to cues encountered in the host. the pathology of melioidosis indicates that b. pseudomallei encounter host microenvironme ... | 2011 | 21537012 |
| improved culture-based detection and quantification of burkholderia pseudomallei from soil. | environmental surveillance of the gram-negative soil bacterium burkholderia pseudomallei, the aetiological agent of melioidosis, is important in order to define human populations and livestock at risk of acquiring the infection. this study aimed to develop a more sensitive method for the detection of b. pseudomallei from soil samples in endemic areas compared with the currently used culture method based on soil dispersion in water. we report the development of a new protocol that involves soil d ... | 2011 | 21543099 |
| burkholderia pseudomallei-induced expression of a negative regulator, sterile-{alpha} and armadillo motif (sarm) containing protein, in mouse macrophages: a possible mechanism for suppression of myd88-independent pathway. | burkholderia pseudomallei, a causative agent of melioidosis, is a gram-negative facultative intracellular bacterium that can survive and multiply in macrophages. previously we demonstrated that b. pseudomallei failed to activate gene expression downstream of myd88-independent pathway, particularly the expression of ifn-β and inducible nitric oxide synthase (inos), leading to the inability of macrophages to kill this bacterium. in the present report, we extended our study to show that b. pseudoma ... | 2011 | 21555400 |
| melioidosis: a clinical overview. | introduction melioidosis, an infection caused by the environmental gram-negative bacillus burkholderia pseudomallei, has emerged as an important cause of morbidity and mortality in southeast asia and northern australia. sources of data a review of the literature using pubmed. areas of agreement approaches to diagnosis and antimicrobial therapy. areas of controversy whether seroconversion signals the presence of a quiescent bacterial focus and an increase in long-term risk of melioidosis. areas t ... | 2011 | 21558159 |
| pulmonary melioidosis in cambodia: a prospective study. | abstract: background: melioidosis is a disease caused by burkholderia pseudomallei and considered endemic in south-east asia but remains poorly documented in cambodia. we report the first series of hospitalized pulmonary melioidosis cases identified in cambodia describing clinical characteristics and outcomes. methods: we characterized cases of acute lower respiratory infections (alri) that were identified through surveillance in two provincial hospitals. severity was defined by systolic blood p ... | 2011 | 21569563 |
| production and characterization of chimeric monoclonal antibodies against burkholderia pseudomallei and b. mallei using the dhfr expression system. | burkholderia pseudomallei (bp) and b. mallei (bm) are closely related gram-negative, facultative anaerobic bacteria which cause life-threatening melioidosis in human and glanders in horse, respectively. our laboratory has previously generated and characterized more than 100 mouse monoclonal antibodies (mabs) against bp and bm, according to in vitro and in vivo assay. in this study, 3 mabs (bp7 10b11, bp7 2c6, and bp1 7f7) were selected to develop into chimeric mouse-human monoclonal antibodies ( ... | 2011 | 21573027 |
| the structure of a burkholderia pseudomallei immunophilin-inhibitor complex reveals new approaches to antimicrobial development. | macrophage infectivity potentiators (mips) are a subset of immunophilins associated with virulence in a range of micro-organisms. these proteins possess prolyl-peptide isomerase activity and are inhibited by drugs including rapamycin and tacrolimus. we determined the structure of the mip homologue (bpml1) from the human pathogen and biowarfare threat burkholderia pseudomallei by nuclear magnetic resonance and x-ray crystallography. the crystal structure suggests that key catalytic residues in th ... | 2011 | 21574961 |
| in vitro activity of bal30072 against burkholderia pseudomallei. | burkholderia pseudomallei is an intrinsically antibiotic-resistant category b priority pathogen and the aetiological agent of melioidosis. treatment of b. pseudomallei infection is biphasic and lengthy in order to combat the acute and chronic phases of the disease. acute-phase treatment preferably involves an intravenous cephalosporin (ceftazidime) or a carbapenem (imipenem or meropenem). in this study, the anti-b. pseudomallei efficacy of a new monosulfactam, bal30072, was tested against labora ... | 2011 | 21596528 |
| mucosal immunization with liposome-nucleic acid adjuvants generates effective humoral and cellular immunity. | development of effective new mucosal vaccine adjuvants has become a priority with the increase in emerging viral and bacterial pathogens. we previously reported that cationic liposomes complexed with non-coding plasmid dna (cldc) were effective parenteral vaccine adjuvants. however, little is known regarding the ability of liposome-nucleic acid complexes to function as mucosal vaccine adjuvants, or the nature of the mucosal immune responses elicited by mucosal liposome-nucleic acid adjuvants. to ... | 2011 | 21600950 |
| flagellar glycosylation in burkholderia pseudomallei and burkholderia thailandensis. | glycosylation of proteins is known to impart novel physical properties and biological roles to proteins from both eukaryotes and prokaryotes. in this study, gel based glycoproteomics were used to identify glycoproteins of the potential bio-threat agent burkholderia pseudomallei and the closely related but non-pathogenic b. thailandensis. top-down and bottom-up ms analysis identified that the flagellin proteins of both species were post-translationally modified by novel glycans. analysis of prote ... | 2011 | 21602339 |
| development and application of a cellular, gain-of-signal, bioluminescent reporter screen for inhibitors of type ii secretion in pseudomonas aeruginosa and burkholderia pseudomallei. | the type ii secretion (t2s) system in gram-negative bacteria comprises the sec and tat pathways for translocating proteins into the periplasm and an outer membrane secretin for transporting proteins into the extracellular space. to discover sec/tat/t2s pathway inhibitors as potential new therapeutics, the authors used a pseudomonas aeruginosa bioluminescent reporter strain responsive to seca depletion and inhibition to screen compound libraries and characterize the hits. the reporter strain plac ... | 2011 | 21602485 |
| spei restriction enzyme displays greater discriminatory power than xbai enzyme does in a pulsed-field gel electrophoresis study on 146 clinical burkholderia pseudomallei isolates. | restriction enzymes spei and xbai were used in a pulsed-field gel electrophoresis (pfge) study for molecular characterization of 146 clinical burkholderia pseudomallei isolates. the pfge parameters were optimized to enable comparable, reproducible, and robust results. the optimized parameters for both spei and xbai restriction enzymes used in this study were 200 v and a pulse time of 5 to 65 s for a 28-h runtime. using spei, 9 different clusters were identified, whereas 6 clusters were identifie ... | 2011 | 21617308 |
| chlorine dioxide inactivation of bacterial threat agents. | aims: to evaluate the efficacy of chlorine dioxide (clo(2) ) against seven species of bacterial threat (bt) agents in water. methods and results: two strains of bacillus anthracis spores, yersinia pestis, francisella tularensis, burkholderia pseudomallei, burkholderia mallei, and brucella species were each inoculated into a clo(2) solution with an initial concentration of 2·0 mg l(-1) (spores only) and 0·25 mg l(-1) (all other bacteria) at ph 7 or 8, 5°c or 25°c. at 0·25 mg l(-1) in potable wa ... | 2011 | 21623848 |
| the aftermath of the western australian melioidosis outbreak. | abstract. melioidosis became a notifiable disease in western australia (wa) 2 years after the west kimberley melioidosis outbreak. two cases of melioidosis caused by the outbreak genotype of burkholderia pseudomallei (national collection of type cultures [nctc] 13177) occurred in 1998 and 1999 in persons who visited the outbreak location at the time. no other infections caused by the outbreak strain have been recorded in wa since that time, despite an average of four culture-positive cases per y ... | 2011 | 21633018 |
| repeat blood culture positive for b. pseudomallei indicates an increased risk of death from melioidosis. | abstract. melioidosis, a bacterial infection caused by burkholderia pseudomallei, is notoriously difficult to cure despite appropriate antimicrobial therapy and has a mortality rate of up to 40%. we demonstrate that a blood culture positive for b. pseudomallei taken at the end of the first and/or second week after hospitalization for melioidosis is a strong prognostic factor for death (adjusted odds ratio = 4.2, 95% confidence interval = 2.1-8.7, p < 0.001 and adjusted odds ratio = 2.6, 95% conf ... | 2011 | 21633019 |
| the use of positive serological tests as evidence of exposure to burkholderia pseudomallei. | | 2011 | 21633045 |
| melioidosis of the extremities in brunei darussalam. | introduction: melioidosis caused by burkholderia pseudomallei is an infectious disease endemic to southeast asia and northern australia. it has a broad spectrum of clinical manifestations and high mortality, and can mimic other infectious diseases. the aim of this study was to review cases of melioidosis of the extremities in brunei darussalam. methods: culture-positive cases for burkholderia pseudomallei in raja isteri pengiran anak saleha hospital were identified from records in the microbiolo ... | 2011 | 21633768 |
| rapid identification of burkholderia pseudomallei and burkholderia mallei by fluorescence in situ hybridization (fish) from culture and paraffin-embedded tissue samples. | we evaluated newly developed probes for rapid identification of burkholderia (b.) pseudomallei and b. mallei and differentiation from b. thailandensis by fluorescence in situ hybridization (fish). fish correctly identified 100% of the tested b. pseudomallei (11), b. mallei (11), and b. thailandensis (1) strains, excluded 100% of all tested negative controls (61), and allowed demonstration of b. pseudomallei infection in a paraffin-embedded spleen tissue sample of an experimentally infected mouse ... | 2011 | 21658996 |
| superoxide dismutase c is required for intracellular survival and virulence of burkholderia pseudomallei. | burkholderia pseudomallei is an intracellular pathogen and the causative agent of melioidosis, a life-threatening disease of humans. within host cells, superoxide is an important mediator of pathogen killing. in this study, we have identified the b. pseudomallei k96243 sodc gene, shown that it has superoxide dismutase activity, and constructed an allelic deletion mutant of this gene. compared with the wild-type, the mutant was more sensitive to killing by extracellular superoxide, but not to sup ... | 2011 | 21659326 |
| regulation of type vi secretion system during burkholderia pseudomallei infection. | type iii and type vi secretion systems (t3sss and t6sss, respectively) are critical virulence determinants in several gram-negative pathogens. in burkholderia pseudomallei, the t3ss-3 and t6ss-1 clusters have been implicated in bacterial virulence in mammalian hosts. we recently discovered a regulatory cascade that coordinately controls the expression of t3ss-3 and t6ss-1. bsan is a central regulator located within t3ss-3 for the expression of t3ss-3 effectors and regulators for t6ss-1 such as v ... | 2011 | 21670170 |
| melioidosis imported from west africa to europe. | abstract. we report the first case of imported melioidosis in spain from a diabetic immigrant who visited west africa during the rainy season. because of the unusual presentation of this disease in africa, clinical and microbiological diagnosis of imported melioidosis from this continent can be very elusive. | 2011 | 21813848 |
| autotransporters and their role in the virulence of burkholderia pseudomallei and burkholderia mallei. | burkholderia pseudomallei and burkholderia mallei are closely related gram-negative bacteria responsible for the infectious diseases melioidosis and glanders, respectively. autotransporters (ats) comprise a large and diverse family of secreted and outer membrane proteins that includes virulence-associated invasins, adhesins, proteases, and actin-nucleating factors. the b. pseudomallei k96243 genome contains 11 predicted ats, eight of which share homologs in the b. mallei atcc 23344 genome. this ... | 2011 | 21811486 |
| the burkholderia pseudomallei {delta}asd mutant exhibits attenuated intracellular infectivity and imparts protection against acute inhalation melioidosis in mice. | burkholderia pseudomallei, the cause of serious and life threatening diseases in humans, is of national biodefense concern because of its potential use as a bioterrorism agent. this microbe is listed as a select agent by the cdc, therefore, development of vaccines is of significant importance. here, we further investigated the growth characteristics of a recently created b. pseudomallei 1026b ?asd mutant in vitro, in a cell model, and in an animal model of infection. the mutant was typified by a ... | 2011 | 21807903 |
| highly sensitive direct detection and quantification of burkholderia pseudomallei in environmental soil samples using real-time pcr. | the soil bacterium and potential biothreat agent burkholderia pseudomallei causes the infectious disease melioidosis, which is naturally acquired through environmental contact with the bacterium. environmental detection of b. pseudomallei represents the basis for the development of a geographical risk map to humans and livestock. the aim of the present study was to develop a highly sensitive culture-independent dna-based method that allows direct quantification of b. pseudomallei from soil. we e ... | 2011 | 21803915 |
| endovascular therapy for infected aortic aneurysms. | objective: to determine the outcome of endovascular therapy for an infected aortic aneurysm in patients with or without aorto-aerodigestive/aortocaval fistulas. methods: from september 2005 to may 2010, 21 patients, 17 abdominal and four thoracic infected aortic aneurysms were treated with an endovascular stent graft at songklanagarind hospital, thailand. five patients presented with fistula complications, 1 aortoesophageal, 1 aortobronchial, 1 aortocaval, and 2 aortoenteric fistulas. lifelong a ... | 2011 | 21802238 |
| neutrophils are the predominant cell-type to associate with burkholderia pseudomallei in a balb/c mouse model of respiratory melioidosis. | a variety of studies have implicated neutrophils and the rapid induction of cytokine in the host response in melioidosis. here a balb/c mouse model of infection with aerosolised burkholderia pseudomalleik96243 has been used to understand the immune response to infection in this model and verify other infection models that show rapid growth of bacteria, colonisation of tissues and periphery, induction of cytokines and influx of neutrophils. uniquely, this study has also determined the association ... | 2011 | 21798336 |
| combining vaccination and postexposure cpg therapy provides optimal protection against lethal sepsis in a biodefense model of human melioidosis. | the gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis, a major cause of lethal sepsis and morbidity in endemic areas of southeast asia and a potential bioterrorism threat. we have used susceptible balb/c mice to evaluate the potential of targeting vaccination and generic immunotherapy to the lung for optimal protection against respiratory challenge. intranasal vaccination with live attenuated b. pseudomallei increased survival and induced interferon-?-secret ... | 2011 | 21791666 |
| isolation and characterization of a novel virulent podovirus which infects burkholderia pseudomallei. | abstract: burkholderia pseudomallei is a saprophytic soil bacterium and the etiological agent that causes melioidosis. it is naturally resistant to many antibiotics and therefore is difficult to treat. bacteriophages may provide an alternative source of treatment. we have isolated and characterised the bacteriophage phi bp-amp1. the phage is a member of the podoviridae family and has a genome size of ~ 45 kb. molecular data based on the gene which encodes for the phage tail tubular protein sugge ... | 2011 | 21791081 |
| improvement of anti-burkholderia mouse monoclonal antibody from various phage-displayed single-chain antibody libraries. | to improve anti-burkholderia monoclonal antibody (mab) binding affinity, six single chain variable fragments (scfvs) constructed previously were used as scaffolds to construct large highly-diversified phage-displayed mouse scfv random and domain libraries. first, we employed random mutagenesis to introduce random point mutations into entire variable regions, generating six random libraries. additionally, the oligonucleotide-directed mutagenesis was targeted on complementarity-determining region ... | 2011 | 21787781 |
| burkholderia pseudomallei-induced cell fusion in u937 macrophages can be inhibited by monoclonal antibodies against host cell surface molecules. | burkholderia pseudomallei induces the formation of multinucleated giant cells in cell monolayers. after infection of human macrophage-like u937 cells with b. pseudomallei, addition of monoclonal antibodies against integrin-associated protein (cd47), e-selectin (cd62e), a fusion regulatory protein (cd98), and e-cadherin (cd324) suppressed multinucleated giant cells in a concentration-dependent manner while monoclonal antibodies against other surface molecules did not inhibit fusion despite bindin ... | 2011 | 21784167 |
| antimicrobial activity of cathelicidin peptides against burkholderia pseudomallei, the causative agent of melioidosis. | | 2011 | 21782393 |
| toll-like receptor 4 region genetic variants are associated with susceptibility to melioidosis. | melioidosis is a tropical infection caused by the gram-negative soil saprophyte burkholderia pseudomallei. despite broad exposure of northeastern thais, disease develops in only a small proportion of individuals. although diabetes is a risk factor, the mechanisms of host susceptibility to melioidosis are still poorly understood. we postulated that toll-like receptors (tlrs) regulate host susceptibility to disease, and that genetic variation in tlrs is associated with melioidosis. we analyzed the ... | 2011 | 21776015 |
| in vitro activity of sitafloxacin against burkholderia pseudomallei. | | 2011 | 21775108 |