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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.201021152057
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 ...201021170972
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 ...201021172353
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- ...201021177905
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 ...201021179405
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 ...201021182082
pathema: a clade-specific bioinformatics resource center for pathogen research.pathema (http://pathema.jcvi.org) is one of the eight bioinformatics resource centers (brcs) funded by the national institute of allergy and infectious disease (niaid) designed to serve as a core resource for the bio-defense and infectious disease research community. pathema strives to support basic research and accelerate scientific progress for understanding, detecting, diagnosing and treating an established set of six target niaid category a-c pathogens: category a priority pathogens; bacillu ...201019843611
the clinical profile and predictors of mortality in patients with melioidosis in south india.melioidosis is an underdiagnosed and underreported disease in india with protean clinical manifestations. mortality in this study population was 17%. the predominant risk factor for melioidosis was diabetes mellitus. multifocal disease was present in 66% and pulmonary involvement in 61% of patients. in a country like india where the conditions are conducive for endemic melioidosis and due to the clinical similarity of melioidosis to diseases like tuberculosis, it is essential for clinicians to h ...201019850605
urokinase receptor is necessary for bacterial defense against pneumonia-derived septic melioidosis by facilitating phagocytosis.urokinase receptor (urokinase-type plasminogen activator receptor [upar], cd87), a gpi-anchored protein, is considered to play an important role in inflammation and fibrinolysis. the gram-negative bacterium burkholderia pseudomallei is able to survive and replicate within leukocytes and causes melioidosis, an important cause of pneumonia-derived community-acquired sepsis in southeast asia. in this study, we investigated the expression and function of upar both in patients with septic melioidosis ...201020142364
distribution of melioidosis cases and viable burkholderia pseudomallei in soil: evidence for emerging melioidosis in taiwan.a survey for the prevalence if burkholderia pseudomallei in soil in taiwan found that its incidence is comparable to that in other regions of the world where melioidosis is endemic. the presence of identical genetic patterns among the clinical and environmental isolates evaluated suggested a link between the pathogens present in contaminated soil and the emergence of indigenous melioidosis.201020147639
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.201020964837
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.201020965890
[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.201020979813
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 ...201021035394
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 ...201021036839
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 ...201021041491
cerebral abscess and calvarial osteomyelitis due to burkholderia pseudomallei. 201021045524
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.201021048270
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 ...201021073038
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 ...201021073065
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 ...201021075883
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 ...201021078354
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 ...201021080156
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 ...201021088051
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 ...201021091532
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 ...201021103048
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.201021110886
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 ...201021114871
lipopolysaccharide from burkholderia thailandensis e264 provides protection in a murine model of melioidosis.burkholderia thailandensis is a less virulent close relative of burkholderia pseudomallei, a cdc category b biothreat agent. we have previously shown that lipopolysaccharide (lps) extracted from b. pseudomallei can provide protection against a lethal challenge of b. pseudomallei in a mouse model of melioidosis. sugar analysis on lps from b. thailandensis strain e264 confirmed that this polysaccharide has a similar structure to lps from b. pseudomallei. mice were immunised with lps from b. thaila ...201020837078
formulation and immunogenicity studies of type iii secretion system needle antigens as vaccine candidates.bacterial infections caused by shigella flexneri, salmonella typhimurium, and burkholderia pseudomallei are currently difficult to prevent due to the lack of a licensed vaccine. here we present formulation and immunogenicity studies for the three type iii secretion system (ttss) needle proteins mxih(δ5), prgi(δ5), and bsal(δ5) (each truncated by five residues at its c terminus) as potential candidates for vaccine development. these antigens are found to be thermally stabilized by the presence of ...201020845448
formulation and immunogenicity of a potential multivalent type iii secretion system-based protein vaccine.the virulence of many pathogenic gram-negative bacteria is dependent upon their type iii secretion (tts) systems. here, we discuss initial formulation studies of five tts needle tip proteins ipad (shigella flexneri), bipd (burkholderia pseudomallei), sipd (salmonella spp.), lcrv (yersinia spp.), and pcrv (pseudomonas aeruginosa) as targets for subunit vaccines. excipient screening and subsequent assays lead to the selection of 10% sucrose and 5% dextrose as an optimal stabilizer combination for ...201020845449
melioidosis: advances in diagnosis and treatment.melioidosis is an infectious disease caused by the soil-associated gram-negative bacterium burkholderia pseudomallei. this review summarizes the evidence underlying current antibiotic regimens and discusses future strategies to reduce mortality.201020847695
application of a non-species dependent elisa for the detection of antibodies in sera of burkholderia pseudomallei-immunized goats.a modified, non-species dependent elisa was performed to detect antibodies in sera of burkholderia pseudomallei-immunized goats using protein g- or protein a-peroxidase conjugates. the rise of antibody titers during the immunization period exhibited corresponding results by modified elisa comparison to conventional elisa and the iha. regarding the increase of antibody levels from the pre-immunized baseline to the post-immunized status, the antibody titer detected by modified elisa was higher tha ...201020849887
the bacterial effector cif interferes with scf ubiquitin ligase function by inhibiting deneddylation of cullin1.cycle inhibiting factor (cif) is one of the effectors delivered into epithelial cells by enteropathogenic escherichia coli (epec) and enterohemorrhagic escherichia coli (ehec) via the type iii secretion system (ttss). cif family proteins, which inhibit host cell-cycle progression via mechanisms not yet precisely understood, are highly conserved among epec, ehec, yersinia pseudotuberculosis, photorhabdus luminescens and burkholderia pseudomallei. levels of several proteins relevant to cell-cycle ...201020850415
stable, site-specific fluorescent tagging constructs optimized for burkholderia species.several vectors that facilitate stable fluorescent labeling of burkholderia pseudomallei and burkholderia thailandensis were constructed. these vectors combined the effectiveness of the mini-tn7 site-specific transposition system with fluorescent proteins optimized for burkholderia spp., enabling bacterial tracking during cellular infection.201020851961
gamma interferon supplementation for melioidosis. 201020852188
structure of a burkholderia pseudomallei trimeric autotransporter adhesin head.pathogenic bacteria adhere to the host cell surface using a family of outer membrane proteins called trimeric autotransporter adhesins (taas). although taas are highly divergent in sequence and domain structure, they are all conceptually comprised of a c-terminal membrane anchoring domain and an n-terminal passenger domain. passenger domains consist of a secretion sequence, a head region that facilitates binding to the host cell surface, and a stalk region.201020862217
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.201020920184
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 ...201020951592
expression and function of macrophage migration inhibitory factor (mif) in melioidosis.macrophage migration inhibitory factor (mif) has emerged as a pivotal mediator of innate immunity and has been shown to be an important effector molecule in severe sepsis. melioidosis, caused by burkholderia pseudomallei, is an important cause of community-acquired sepsis in southeast-asia. we aimed to characterize the expression and function of mif in melioidosis.201020169062
growing burkholderia pseudomallei in biofilm stimulating conditions significantly induces antimicrobial resistance.burkholderia pseudomallei, a gram-negative bacterium that causes melioidosis, was reported to produce biofilm. as the disease causes high relapse rate when compared to other bacterial infections, it therefore might be due to the reactivation of the biofilm forming bacteria which also provided resistance to antimicrobial agents. however, the mechanism on how biofilm can provide tolerance to antimicrobials is still unclear.201020169199
immunotherapy markedly increases the effectiveness of antimicrobial therapy for treatment of burkholderia pseudomallei infection.burkholderia pseudomallei is a soil bacterium that is endemic in southeast asia and northern australia and that can cause both acutely lethal pneumonia and chronic systemic infections in humans. the effective treatment of infection with b. pseudomallei requires rapid diagnosis and prolonged treatment with high doses of antimicrobials, and even with appropriate antibiotic therapy, patient relapses are common. thus, new approaches to the treatment of b. pseudomallei infections are needed. in the p ...201020176901
cpg oligodeoxyribonucleotides protect mice from burkholderia pseudomallei but not francisella tularensis schu s4 aerosols.abstract: studies have shown that cpg oligodeoxyribonucleotides (odn) protect mice from various bacterial pathogens, including burkholderia pseudomallei and francisella tularensis live vaccine strain (lvs), when administered before parenteral challenge. given the potential to develop cpg odn as a pre-treatment for multiple bacterial biological warfare agents, we examined survival, histopathology, and cytokine data from cpg odn-treated c57bl/6 mice to determine whether previously-reported protect ...201020181102
in vitro activity of biapenem against burkholderia pseudomallei. 201020188524
present and future therapeutic strategies for melioidosis and glanders.burkholderia pseudomallei and burkholderia mallei are the causative agents of melioidosis and glanders, respectively. both gram-negative pathogens are endemic in many parts of the world. although natural acquisition of these pathogens is rare in the majority of countries, these bacteria have recently gained much interest because of their potential as bioterrorism agents. in modern times, their potential destructive impact on public health has escalated owing to the ability of these pathogens to ...201020192686
cdpa is a burkholderia pseudomallei cyclic di-gmp phosphodiesterase involved in autoaggregation, flagellum synthesis, motility, biofilm formation, cell invasion, and cytotoxicity.cyclic diguanylic acid (c-di-gmp) is an intracellular signaling molecule involved in regulation of cellular functions such as motility, biofilm formation and virulence. intracellular level of c-di-gmp is controlled through opposing diguanylate cyclase (dgc) and phosphodiesterase (pde) activities of ggdef and eal domain proteins, respectively. we report the identification and characterization of cdpa, a gene encoding a protein containing an eal domain in the gram-negative soil bacillus and human ...201020194589
mycotic iliac aneurysm associated with burkholderia pseudomallei. 201019897393
inactivation of burkholderia cepacia complex phage ks9 gp41 identifies the phage repressor and generates lytic virions.the burkholderia cepacia complex (bcc) is made up of at least 17 species of gram-negative opportunistic bacterial pathogens that cause fatal infections in patients with cystic fibrosis and chronic granulomatous disease. ks9 (vb_bcens_ks9), one of a number of temperate phages isolated from bcc species, is a prophage of burkholderia pyrrocinia lmg 21824. transmission electron micrographs indicate that ks9 belongs to the family siphoviridae and exhibits the b1 morphotype. the 39,896-bp ks9 genome, ...201019939932
user-loaded slipchip for equipment-free multiplexed nanoliter-scale experiments.this paper describes a microfluidic approach to perform multiplexed nanoliter-scale experiments by combining a sample with multiple different reagents, each at multiple mixing ratios. this approach employs a user-loaded, equipment-free slipchip. the mixing ratios, characterized by diluting a fluorescent dye, could be controlled by the volume of each of the combined wells. the slipchip design was validated on an approximately 12 nl scale by screening the conditions for crystallization of glutaryl ...201020000708
growth-related changes in intracellular spermidine and its effect on efflux pump expression and quorum sensing in burkholderia pseudomallei.the burkholderia pseudomallei bpeab-oprb resistance-nodulation-division (rnd) family pump effluxes aminoglycoside and macrolide antibiotics as well as acylhomoserine lactones (ahls) involved in quorum sensing. expression of bpea-lacz was cell density-dependent and was inducible in the presence of these compounds. intracellular levels of spermidine and n-acetylspermidine increased with cell density in wild-type b. pseudomallei khw, but were always lower in the bpeab pump mutant at all growth phas ...201020035006
the survival of burkholderia pseudomallei in liquid media.we studied the effect of environmental parameters on the survival of burkholderia pseudomallei. there was a small increase in bacterial count for up to 28 days in sterilized distilled water or rain water, in water at 20 degrees c or 40 degrees c, and in buffered solutions of ph 4 or higher. counts of culturable b. pseudomallei declined at ph 3, in the presence of seawater or water with concentrations of 4% salt or higher, and under refrigeration. the morphological appearances of b. pseudomallei ...201020065001
changing spectrum of microbiology of liver abscess: now klebsiella, next burkholderia pseudomallei. 201020079999
sequence polymorphism and pcr-restriction fragment length polymorphism analysis of the flagellin gene of burkholderia pseudomallei.four flagellin allelic types (i to iv) of burkholderia pseudomallei were identified based on their sequence variation and restriction fragment length polymorphism (rflp) analysis of the amplified flagellin gene. flagellin allelic type i was the most predominantly (75.0%) found among the 100 clinical isolates of b. pseudomallei investigated in this study.201020089759
within-host evolution of burkholderia pseudomallei in four cases of acute melioidosis.little is currently known about bacterial pathogen evolution and adaptation within the host during acute infection. previous studies of burkholderia pseudomallei, the etiologic agent of melioidosis, have shown that this opportunistic pathogen mutates rapidly both in vitro and in vivo at tandemly repeated loci, making this organism a relevant model for studying short-term evolution. in the current study, b. pseudomallei isolates cultured from multiple body sites from four thai patients with disse ...201020090837
spatial analysis of melioidosis distribution in a suburban area.burkholderia pseudomallei, the causative agent of melioidosis is associated with soil. this study used a geographic information system (gis) to determine the spatial distribution of clinical cases of melioidosis in the endemic suburban region of townsville in australia. a total of 65 cases over the period 1996-2008 were plotted using residential address. two distinct groupings were found. one was around the base of a hill in the city centre and the other followed the old course of a major waterw ...201020092666
radiological manifestations of melioidosis.melioidosis is a serious infection that is associated with high mortality. it is due to a gram-negative bacterium, burkholderia pseudomallei which is an environmental saprophyte found in wet soils. melioidosis is endemic to northern australia and the southeast asia. however, there is now increasing number of reports of imported cases to regions where this infection has not been previously encountered. almost any organ can be affected. like many other conditions, radiological imaging is an integr ...201020103424
identification of tomato plant as a novel host model for burkholderia pseudomallei.burkholderia pseudomallei is the causative agent for melioidosis, a disease with significant mortality and morbidity in endemic regions. its versatility as a pathogen is reflected in its relatively huge 7.24 mb genome and the presence of many virulence factors including three type three secretion systems known as t3ss1, t3ss2 and t3ss3. besides being a human pathogen, it is able to infect and cause disease in many different animals and alternative hosts such as c. elegans.201020109238
innate immune detection of the type iii secretion apparatus through the nlrc4 inflammasome.the mammalian innate immune system uses toll-like receptors (tlrs) and nod-lrrs (nlrs) to detect microbial components during infection. often these molecules work in concert; for example, the tlrs can stimulate the production of the proforms of the cytokines il-1beta and il-18, whereas certain nlrs trigger their subsequent proteolytic processing via caspase 1. gram-negative bacteria use type iii secretion systems (t3ss) to deliver virulence factors to the cytosol of host cells, where they modula ...201020133635
melioidosis and the vacuum-assisted closure device: a rare cause of a discharging neck wound, and a new approach to management.we report a case of melioidosis presenting as a discharging neck abscess, and we describe the use of a vacuum-assisted closure device in its management.201020219147
role of a burkholderia pseudomallei polyphosphate kinase in an oxidative stress response, motilities, and biofilm formation.burkholderia pseudomallei, a motile and rod gram-negative bacterium, is the causative agent of melioidosis. the bacterium is an intracellular pathogen and that motility is generally crucial for their survival in a natural environment and for systemic infection inside a host. we report here a role of b. pseudomallei polyphosphate kinase in virulence, such as an oxidative stress response, motilities and biofilm formation. the polyphosphate kinase (ppk) mutant is susceptible to hydrogen peroxide in ...201020221731
imported melioidosis in danish travellers: a diagnostic challenge.infections with burkholderia pseudomallei (melioidosis) are rare events in scandinavian countries, but the bacterium may be contracted during travel to endemic areas, i.e. southeast asia (especially thailand) and northern australia. here, 5 travel-related cases occurring within the last 3 y in denmark are reported, with particular emphasis on diagnostic and therapeutic challenges posed to health staff with little experience in the management of melioidosis. a newly developed b. pseudomallei-spec ...201020297927
structural characterization of burkholderia pseudomallei adenylate kinase (adk): profound asymmetry in the crystal structure of the 'open' state.in all organisms adenylate kinases (adks) play a vital role in cellular energy metabolism and nucleic acid synthesis. due to differences in catalytic properties between the adks found in prokaryotes and in the cytoplasm of eukaryotes, there is interest in targeting this enzyme for new drug therapies against infectious bacterial agents. here we report the 2.1a resolution crystal structure for the 220-residue adk from burkholderia pseudomallei (bpadk), the etiological agent responsible for the inf ...201020331978
continuing evolution of burkholderia mallei through genome reduction and large-scale rearrangements.burkholderia mallei (bm), the causative agent of the predominately equine disease glanders, is a genetically uniform species that is very closely related to the much more diverse species burkholderia pseudomallei (bp), an opportunistic human pathogen and the primary cause of melioidosis. to gain insight into the relative lack of genetic diversity within bm, we performed whole-genome comparative analysis of seven bm strains and contrasted these with eight bp strains. the bm core genome (shared by ...201020333227
suppression of host innate immune response by burkholderia pseudomallei through the virulence factor tssm.burkholderia pseudomallei is a gram-negative saprophyte that is the causative agent of melioidosis, a severe infectious disease endemic in northern australia and southeast asia. this organism has sparked much scientific interest in the west because of its classification as a potential bioterrorism agent by the u.s. centers for disease control and prevention. however, relatively little is known about its pathogenesis. we demonstrate that b. pseudomallei actively inhibits nf-kappab and type i ifn ...201020335533
development and evaluation of polymerase chain reaction assay to detect burkholderia genus and to differentiate the species in clinical specimens.molecular-based techniques are becoming desirable as tools for identification of infectious diseases. amongst the burkholderia spp., there is a need to differentiate burkholderia pseudomallei from burkholderia cepacia, as misidentification could lead to false treatment of patients. in this study, conventional pcr assay targeting three genes was developed. primers were designed for the amplification of burkholderia genus-specific groel gene, b. pseudomallei-specific mpra gene and b. cepacia-speci ...201020345378
identification of a regulatory cascade controlling type iii secretion system 3 gene expression in burkholderia pseudomallei.a major and critical virulence determinant of many gram-negative bacterial pathogens is the type iii secretion systems (t3ss). t3ss3 in burkholderia pseudomallei is critical for bacterial virulence in mammalian infection models but its regulation is unknown. b. pseudomallei is the causative agent of melioidosis, a potentially fatal disease endemic in southeast asia and northern australia. while screening for bacterial transposon mutants with a defective t3ss function, we discovered a tetr family ...201020345664
susceptibility of burkholderia pseudomallei to tigecycline and other antimicrobials. 201020356698
the man with the boggy head: cranial melioidosis.melioidosis is known to cause abscesses in various organs, including the cranium, though less commonly. we present a patient with scalp abscess and subdural empyema that was visible on computed tomography of the brain. the neurosurgical drainage grew burkholderia pseudomallei. despite our best effort to treat the patient using parenteral antibiotics and surgical drainage, the patient did not survive.201020358143
a genomic survey of positive selection in burkholderia pseudomallei provides insights into the evolution of accidental virulence.certain environmental microorganisms can cause severe human infections, even in the absence of an obvious requirement for transition through an animal host for replication ("accidental virulence"). to understand this process, we compared eleven isolate genomes of burkholderia pseudomallei (bp), a tropical soil microbe and causative agent of the human and animal disease melioidosis. we found evidence for the existence of several new genes in the bp reference genome, identifying 282 novel genes su ...201020368977
a burkholderia pseudomallei deltapurm mutant is avirulent in immunocompetent and immunodeficient animals: candidate strain for exclusion from select-agent lists.burkholderia pseudomallei causes the disease melioidosis in humans and is classified as a category b select agent. research utilizing this pathogen is highly regulated in the united states, and even basic studies must be conducted in biosafety level 3 (bsl-3) facilities. there is currently no attenuated b. pseudomallei strain available that is excluded from select-agent regulations and can be safely handled at bsl-2 facilities. to address this need, we created bp82 and bp190, which are deltapurm ...201020404077
evaluation of igm elisa using a sonicate and a lipopolysaccharide antigen for the serodiagnosis of melioidosis.melioidosis, caused by burkholderia pseudomallei, has variable manifestations. the disease can present as an acute or a chronic form or localized or disseminated or can remain latent for many years. acute septicaemic melioidosis has a high fatality rate when untreated and therefore, an early diagnosis is critical. lack of testing facilities and of an awareness of the manifestations of the disease makes it likely that it is underreported in india. a sonicate and a lipopolysaccharide (lps) antigen ...201020404465
[tropical pneumonia: pulmonary melioidosis].melioidosis is a disease that is endemic in north australia and southeast asia, caused by burkholderia pseudomallei. this gram-negative organism can affect all organs, but presents most commonly as severe pneumonia. we report a 58-year-old man who presented with a b. pseudomallei pneumonia on his return from thailand. radiography revealed a complete disappearance of symptoms after a 3-week therapy with ceftazidime and doxycycline followed by 4 months of combined amoxicillin-clavulanic acid and d ...201020413195
burkholderia pseudomallei musculoskeletal infections (melioidosis) in india.melioidosis, an infection due to gram negative burkholderia pseudomallei, is an important cause of sepsis in east asia especially thailand and northern australia. it usually causes abscesses in lung, liver, spleen, skeletal muscle and parotids especially in patients with diabetes, chronic renal failure and thalassemia. musculoskeletal melioidosis is not common in india even though sporadic cases have been reported mostly involving soft tissues. during a two-year-period, we had five patients with ...201020419012
fatal burkholderia pseudomallei septicaemia in a patient with diabetes. 201020424312
the structure of sedoheptulose-7-phosphate isomerase from burkholderia pseudomallei reveals a zinc binding site at the heart of the active site.heptoses are found in the surface polysaccharides of most bacteria, contributing to structures that are essential for virulence and antibiotic resistance. consequently, the biosynthetic enzymes for these sugars are attractive targets for novel antibiotics. the best characterized biosynthetic enzyme is gmha, which catalyzes the conversion of sedoheptulose-7-phosphate into d-glycero-d-manno-heptopyranose-7-phosphate, the first step in the biosynthesis of heptose. here, the structure of gmha from b ...201020447408
[melioidosis: the importance of a detailed medical history, including recent travels].a 70-year-old woman was admitted to hospital with fever and signs of bronchopneumonia following a recent visit to southeast asia. she was diagnosed with melioidosis and treated with ceftazidime i.v. for two weeks, followed by oral co-trimoxazol and folinic acid. she recovered and had no recurring disease in the first year following recovery. melioidosis is caused by an infection with burkholderia pseudomallei. clinical presentation can vary, but pneumonia is present in most patients. the diagnos ...201020456806
evaluation of azithromycin, trovafloxacin and grepafloxacin as prophylaxis for experimental murine melioidosis.the efficacies of the azalide azithromycin and the fluoroquinolones trovafloxacin and grepafloxacin for pre- and post-exposure prophylaxis of infection with high or low challenge doses of burkholderia pseudomallei strain 576 were assessed in an experimental mouse model. trovafloxacin and grepafloxacin afforded significant levels of protection, whereas azithromycin was ineffective and potentially detrimental. overall, the data suggest that some fluoroquinolones may have potential utility in proph ...201020462743
pulmonary melioidosis in febrile neutropenia: the rare and deadly duet.we present the first two fulminant cases of pulmonary melioidosis in febrile neutropenic patients with acute and varied presentations seen in our institution and their fatal outcome. a high index of suspicion coupled with microbiological confirmation can facilitate the administration of the appropriate therapy in cases of melioidosis that differ from other bacterial infections in terms of presentation and the response to antimicrobials.201020478984
meropenem dosing in critically ill patients with sepsis receiving high-volume continuous venovenous hemofiltration.use of high ultrafiltrate flow rates with continuous venovenous hemofiltration (cvvhf) in critically ill patients is an emerging setting, for which there are few data to guide drug dosing. the objectives of this study were, firstly, to investigate the pharmacokinetics of meropenem in critically ill patients with severe sepsis who are receiving high-volume cvvhf with high-volume exchanges (> or = 4 liters/h); secondly, to determine whether standard dosing regimens (1,000 mg intravenously [i.v.] e ...201020479205
the bpeab-oprb efflux pump of burkholderia pseudomallei 1026b does not play a role in quorum sensing, virulence factor production, or extrusion of aminoglycosides but is a broad-spectrum drug efflux system.most burkholderia pseudomallei strains are intrinsically aminoglycoside resistant, mainly due to amrab-opra-mediated efflux. rare naturally occurring or genetically engineered mutants lacking this pump are aminoglycoside susceptible despite the fact that they also encode and express bpeab-oprb, which was reported to mediate efflux of aminoglycosides in the singapore strain khw. to reassess the role of bpeab-oprb in b. pseudomallei aminoglycoside resistance, we used mutants overexpressing or lack ...201020498323
bacterial loads and antibody responses in balb/c mice infected with low and high doses of burkholderia pseudomallei.profiles of burkholderia pseudomallei persistence and antibodies in blood, spleen, liver, and lungs of infected balb/c mice were investigated. animals were infected intraperitoneally with low (6 colony-forming units) or high (230 colony-forming units) doses of b. pseudomallei. in the high-dose infected group, bacteria were found by culture in 100% of blood, liver, spleen and lung samples at 24 and 48 hours after infections; blood samples were 100% positive by polymerase chain reaction after 60 h ...201020519607
emergence of pediatric melioidosis in siem reap, cambodia.we describe the first cases of pediatric melioidosis in cambodia. thirty-nine cases were diagnosed at the angkor hospital for children, siem reap, between october 2005 and december 2008 after the introduction of microbiology capabilities. median age was 7.8 years (range = 1.6-16.2 years), 15 cases were male (38%), and 4 cases had pre-existing conditions that may have pre-disposed the patient to melioidosis. infection was localized in 27 cases (69%) and disseminated in 12 cases (31%). eleven case ...201020519608
increasing incidence of human melioidosis in northeast thailand.melioidosis is a serious community-acquired infectious disease caused by the gram-negative environmental bacterium burkholderia pseudomallei. a prospective cohort study identified 2,243 patients admitted to sappasithiprasong hospital in northeast thailand with culture-confirmed melioidosis between 1997 and 2006. these data were used to calculate an average incidence rate for the province of 12.7 cases of melioidosis per 100,000 people per year. incidence increased incrementally from 8.0 (95% con ...201020519609
effective, broad spectrum control of virulent bacterial infections using cationic dna liposome complexes combined with bacterial antigens.protection against virulent pathogens that cause acute, fatal disease is often hampered by development of microbial resistance to traditional chemotherapeutics. further, most successful pathogens possess an array of immune evasion strategies to avoid detection and elimination by the host. development of novel, immunomodulatory prophylaxes that target the host immune system, rather than the invading microbe, could serve as effective alternatives to traditional chemotherapies. here we describe the ...201020523903
the early stage of bacterial genome-reductive evolution in the host.the equine-associated obligate pathogen burkholderia mallei was developed by reductive evolution involving a substantial portion of the genome from burkholderia pseudomallei, a free-living opportunistic pathogen. with its short history of divergence (approximately 3.5 myr), b. mallei provides an excellent resource to study the early steps in bacterial genome reductive evolution in the host. by examining 20 genomes of b. mallei and b. pseudomallei, we found that stepwise massive expansion of is ( ...201020523904
molecular insights into burkholderia pseudomallei and burkholderia mallei pathogenesis.burkholderia pseudomallei and burkholderia mallei are closely related gram-negative bacteria that can cause serious diseases in humans and animals. this review summarizes the current and rapidly expanding knowledge on the specific virulence factors employed by these pathogens and their roles in the pathogenesis of melioidosis and glanders. in particular, the contributions of recently identified virulence factors are described in the context of the intracellular lifestyle of these pathogens. thro ...201020528691
burkholderia pseudomallei is spatially distributed in soil in northeast thailand.melioidosis is a frequently fatal infectious disease caused by the soil dwelling gram-negative bacterium burkholderia pseudomallei. environmental sampling is important to identify geographical distribution of the organism and related risk of infection to humans and livestock. the aim of this study was to evaluate spatial distribution of b. pseudomallei in soil and consider the implications of this for soil sampling strategies.201020532233
involvement of the myd88-independent pathway in controlling the intracellular fate of burkholderia pseudomallei infection in the mouse macrophage cell line raw 264.7.burkholderia pseudomallei is a facultative intracellular gram-negative bacterium which is capable of surviving and multiplying inside macrophages. b. pseudomallei strain srm117, a lps mutant which lacks the o-antigenic polysaccharide moiety, is more susceptible to macrophage killing during the early phase of infection than is its parental wild type strain (1026b). in this study, it was shown that the wild type is able to induce expression of genes downstream of the myd88-dependent (ikappabzeta, ...201020536725
global transcriptional profiling of burkholderia pseudomallei under salt stress reveals differential effects on the bsa type iii secretion system.burkholderia pseudomallei is the causative agent of melioidosis where the highest reported incidence world wide is in the northeast of thailand, where saline soil and water are prevalent. moreover, recent reports indicate a potential pathogenic role for b. pseudomallei in cystic fibrosis lung disease, where an increased sodium chloride (nacl) concentration in airway surface liquid has been proposed. these observations raise the possibility that high salinity may represent a favorable niche for b ...201020540813
association of the melioidosis agent burkholderia pseudomallei with water parameters in rural water supplies in northern australia.we analyzed water parameters and the occurrence of the melioidosis agent burkholderia pseudomallei in 47 water bores in northern australia. b. pseudomallei was associated with soft, acidic bore water of low salinity but high iron levels. this finding aids in identifying water supplies at risk of contamination with this pathogenic bacterium.201020543039
immunization with the recombinant burkholderia pseudomallei outer membrane protein omp85 induces protective immunity in mice.burkholderia pseudomallei is resistant to a wide range of antibiotics, leading to relapse and recrudescence of melioidosis after cessation of antibiotic therapy. more effective immunotherapies are needed for better management of melioidosis. we evaluated the prophylactic potential of the immunogenic outer membrane protein omp85 as a vaccine against murine melioidosis. immunization of balb/c mice with recombinant omp85 (romp85) triggered a th2-type immune response. up to 70% of the immunized anim ...201020546831
isonicotinic acid hydrazide conversion to isonicotinyl-nad by catalase-peroxidases.activation of the pro-drug isoniazid (inh) as an anti-tubercular drug in mycobacterium tuberculosis involves its conversion to isonicotinyl-nad, a reaction that requires the catalase-peroxidase katg. this report shows that the reaction proceeds in the absence of katg at a slow rate in a mixture of inh, nad(+), mn(2+), and o(2), and that the inclusion of katg increases the rate by >7 times. superoxide, generated by either mn(2+)- or katg-catalyzed reduction of o(2), is an essential intermediate i ...201020554537
a high-throughput pipeline for the design of real-time pcr signatures.pathogen diagnostic assays based on polymerase chain reaction (pcr) technology provide high sensitivity and specificity. however, the design of these diagnostic assays is computationally intensive, requiring high-throughput methods to identify unique pcr signatures in the presence of an ever increasing availability of sequenced genomes.201020573238
spectrum of melioidosis in the suburbs of mangalore, s west coast of india.melioidosis is an emerging infection in india. seventeen cases of culture proven melioidosis are reported in this study. the isolation rate was high during the rainy season. except one case, all the patients had diabetes mellitus as an underlying disease. eleven patients improved with ceftazidime or combination therapy and maintenance therapy with doxycycline and cotrimoxazole. the high prevalence of b. pseudomallei in this region is a matter for serious concern.201020578496
burkholderia thailandensis whole cell antigen cross-reacts with b. pseudomallei antibodies from patients with melioidosis in an immunofluorescent assay.an immunofluorescent assay (ifat) using whole cell antigen derived from burkholderia thailandensis used for detection of total antibodies to burkholderia pseudomallei, was found to compare favorably with a previous published report on a b. pseudomallei ifat assay. at a 1:20 cut-off titer, the assay had high sensitivity (98.9%) and satisfactory specificity (92.3%), when tested against sera from 94 patients suspected of melioidosis. sera from 12 patients with culture proven melioidosis gave absolu ...201020578523
melioidosis in southern india: epidemiological and clinical profile.melioidosis, which is mainly prevalent in thailand and australia, has shown an increasing trend in india in the last few years. we carried out a retrospective study of 25 culture-proven adult cases of melioidosis who were admitted to a tertiary care hospital in southern india during june 2001 to september 2007. there was a six-fold increase in the number of cases in 2006 and 2007 as compared to 2001. diabetes mellitus was the predisposing factor in 68% of cases, followed by alcoholism (28%). the ...201020578524
melioidosis and pulmonary tuberculosis co-infection in a diabetic.burkholderia pseudomallei is the causative agent of melioidosis. it is endemic in south east asian countries and north australia. sporadic cases of melioidosis have been reported from several parts of south india. melioidosis may manifest as chronic pneumonia mimicking tuberculosis and generally be seen as a single entity. we report the first case of melioidosis and pulmonary tuberculosis co-infection in a diabetic patient. the causative agents were identified using standard methods and the pati ...201020582178
escape of intracellular shigella from autophagy requires binding to cholesterol through the type iii effector, icsb.type iii secretion systems are present in many pathogenic bacteria and mediate the translocation of bacterial effectors into host cells. identification of host targets of these effectors is crucial for understanding bacterial virulence. icsb, a type iii secretion effector, helps shigella to evade the host autophagy defense system by binding to the autophagy protein, atg5. here, we show that icsb is able to interact specifically with cholesterol. the cholesterol binding domain (cbd) of icsb is lo ...201020599519
burkholderia pseudomallei rpos regulates oxyr and the katg-dpsa operon under conditions of oxidative stress.burkholderia pseudomallei, the causative agent of the potentially fatal tropical disease melioidosis, is known to be highly resistant to oxidative stress although the mechanism of this resistance remains to be fully elucidated. previous studies have shown that an oxyr is involved in the regulation of oxidative stress via the katg and dpsa genes encoding katg and dpsa and that the alternative sigma factor, rpos, plays a critical role in resistance to oxidative stress by regulating katg and kate g ...201020618685
solution conformation and dynamics of exopolysaccharides from burkholderia species.exopolysaccharides (epss) from the burkholderia genus are proposed to be involved in pathological conditions in humans, such as cystic fibrosis and septicemia, as well as in the stability of soil aggregates. hence, considering that the conformational and dynamic aspects of such epss may influence their biological activity, the current work employs a series of molecular dynamics simulations on di-, oligo-, and polysaccharide fragments of three epss, from burkholderia caribensis, burkholderia cepa ...201020633874
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