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clinical outcomes in musculoskeletal involvement of burkholderia pseudomallei infection.musculoskeletal involvement in melioidosis is often seen in conjunction with a disseminated illness. recent reports suggest that operative management of musculoskeletal melioidosis has favourable results. the purpose of this study was to review the patient profile and clinical outcomes of burkholderia pseudomallei infection in the musculoskeletal system.201728861207
mitogen-activated protein kinases (mapks) are modulated during in vitro and in vivo infection with the intracellular bacterium burkholderia pseudomallei.burkholderia pseudomallei is a gram-negative intracellular bacterium that causes the disease melioidosis. the disease can be fatal if left untreated or when antibiotic therapy is delayed and total clearance of the pathogen from the host is often not accomplished with current therapies. thus, new therapeutic approaches for the treatment of infections caused by b. pseudomallei are required. to better understand host responses to b. pseudomallei infection, the activation of key proteins involved in ...201728856457
investigation of host-pathogen interaction between burkholderia pseudomallei and autophagy-related protein lc3 using hydrophobic chromatography-based technique.burkholderia pseudomallei is an intracellular bacteria causing melioidosis, the disease widely disseminates in southeast asia and northern australia. b. pseudomallei has ability to invade various types of host cell and to interfere with host defense mechanisms, such as nitric oxide (no). due to the cross-talk among alternative killing mechanisms in host immune response against invading microbes, autophagy is the molecular mechanism belonging to intracellular elimination of eukaryotic cells that ...201728852470
burkholderia pseudomallei evades nramp1 (slc11a1)- and nadph oxidase-mediated killing in macrophages and exhibits nramp1-dependent virulence gene expression.bacterial survival in macrophages can be affected by the natural resistance-associated macrophage protein 1 (nramp1; also known as solute carrier family 11 member a1 or slc11a1) which localizes to phagosome membranes and transports divalent cations, including iron. little is known about the role of nramp1 in burkholderia infection, in particular whether this differs for pathogenic species like burkholderia pseudomallei causing melioidosis or non-pathogenic species like burkholderia thailandensis ...201728848712
host-adaptation of burkholderia pseudomallei alters metabolism and virulence: a global proteome analysis.little is known about the evolution, adaptation and pathogenesis of burkholderia pseudomallei within host during acute melioidosis infection. melioidosis is a potential life threatening disease contracted through inhalation, ingestion, inoculation or direct entry of the organism into the blood stream via wounds or skin abrasions from contaminated soil and water. environmental b. pseudomallei strain (bp maran ), isolated during a melioidosis outbreak in pahang, malaysia was injected intra-periton ...201728827633
anti-cancer drug hmba acts as an adjuvant during intracellular bacterial infections by inducing type i ifn through sting.the anti-proliferative agent hexamethylene bisacetamide (hmba) belongs to a class of hybrid bipolar compounds developed more than 30 y ago for their ability to induce terminal differentiation of transformed cells. recently, hmba has also been shown to trigger hiv transcription from latently infected cells, via a cdk9/hmba inducible protein-1 dependent process. however, the effect of hmba on the immune response has not been explored. we observed that pretreatment of human peripheral blood mononuc ...201728827286
pacbio but not illumina technology can achieve fast, accurate and complete closure of the high gc, complex burkholderia pseudomallei two-chromosome genome.although pacbio third-generation sequencers have improved the read lengths of genome sequencing which facilitates the assembly of complete genomes, no study has reported success in using pacbio data alone to completely sequence a two-chromosome bacterial genome from a single library in a single run. previous studies using earlier versions of sequencing chemistries have at most been able to finish bacterial genomes containing only one chromosome with de novo assembly. in this study, we compared t ...201728824579
persistent infection due to a small-colony variant of burkholderia pseudomallei leads to pd-1 upregulation on circulating immune cells and mononuclear infiltration in viscera of experimental balb/c mice.melioidosis is a neglected tropical disease endemic across south east asia and northern australia. the etiological agent, burkholderia pseudomallei (b.pseudomallei), is a gram-negative, rod-shaped, motile bacterium residing in the soil and muddy water across endemic regions of the tropical world. the bacterium is known to cause persistent infections by remaining latent within host cells for prolonged duration. reactivation of the recrudescent disease often occurs in elders whose immunity wanes. ...201728820897
differential microrna analyses of burkholderia pseudomallei- and francisella tularensis-exposed hpbmcs reveal potential biomarkers.increasing evidence that micrornas (mirnas) play important roles in the immune response against infectious agents suggests that mirna might be exploitable as signatures of exposure to specific infectious agents. in order to identify potential early mirna biomarkers of bacterial infections, human peripheral blood mononuclear cells (hpbmcs) were exposed to two select agents, burkholderia pseudomallei k96243 and francisella tularensis shu s4, as well as to the nonpathogenic control escherichia coli ...201728791299
nitrate sensing and metabolism inhibit biofilm formation in the opportunistic pathogen burkholderia pseudomallei by reducing the intracellular concentration of c-di-gmp.the opportunistic pathogen burkholderia pseudomallei is a saprophytic bacterium and the causative agent of melioidosis, an emerging infectious disease associated with high morbidity and mortality. although melioidosis is most prevalent during the rainy season in endemic areas, domestic gardens and farms can also serve as a reservoir for b. pseudomallei during the dry season, in part due to irrigation and fertilizer use. in the environment, b. pseudomallei forms biofilms and persists in soil near ...201728790983
a simple laboratory algorithm for diagnosis of melioidosis in resource-constrained areas: a study from north central vietnam.melioidosis may be endemic in many tropical developing countries but diagnosis of the disease is currently unreliable in resource-limited areas. here we aimed to validate a simple and cheap laboratory algorithm for the identification of burkholderia pseudomallei from clinical specimens in parts of vietnam where the disease has not been reported before.201728780059
bipc, a predicted burkholderia pseudomallei type 3 secretion system translocator protein with actin binding activity.burkholderia pseudomallei is an intracellular bacterial pathogen and the causative agent of melioidosis, a severe disease of humans and animals. like other clinically important gram-negative bacteria, fundamental to b. pseudomallei pathogenesis is the bsa type iii secretion system. the bsa system injects bacterial effector proteins into the cytoplasm of target host cells subverting cellular pathways for the benefit of the bacteria. it is required for invasion of non-phagocytic host cells, escape ...201728770177
a case report of co-infection of melioidosis and cutaneous leishmaniasis.leishmaniasis and melioidosis are frequently reported from the north central province of sri lanka. however, only one case of co-infection of the two diseases has been reported to date over the world. this is a case report of a patient who had co-infection with cutaneous leishmaniasis and melioidosis and was successfully treated and recovered from the illness.201728764662
entry, intracellular survival and multinucleated giant cell-forming activity of burkholderia pseudomallei in human primary phagocytic and non-phagocytic cells.the human pathogen burkholderia pseudomallei and the related species burkholderia thailandensis are facultative intracellular bacteria characterized by the ability to escape into the cytosol of the host cell and to stimulate the formation of multinucleated giant cells (mngcs). mngc formation is induced via an unknown mechanism by the bacterial type vi secretion system 5 (t6ss-5), which is an essential virulence factor in both species. despite the vital role of the intracellular life cycle in the ...201728760929
deciphering minimal antigenic epitopes associated with burkholderia pseudomallei and burkholderia mallei lipopolysaccharide o-antigens.burkholderia pseudomallei (bp) and burkholderia mallei (bm), the etiologic agents of melioidosis and glanders, respectively, cause severe disease in both humans and animals. studies have highlighted the importance of bp and bm lipopolysaccharides (lps) as vaccine candidates. here we describe the synthesis of seven oligosaccharides as the minimal structures featuring all of the reported acetylation/methylation patterns associated with bp and bm lps o-antigens (oags). our approach is based on the ...201728740137
epidemiological cut-off value of clinical isolates of burkholderia pseudomallei from northern queensland to meropenem, ceftazidime, trimethoprim/sulfamethoxazole and doxycycline by the microbroth dilution method.melioidosis is caused by the bacterium burkholderia pseudomallei. the most common antibiotics used to treat melioidosis in australia are meropenem, ceftazidime, trimethoprim/sulfamethoxazole (sxt) and doxycycline. the european committee on antimicrobial susceptibility testing (eucast) and clinical and laboratory standards institute (clsi) do not provide standards for assessing the susceptibility of b. pseudomallei for these agents. the international standards organisation (iso) microbroth diluti ...201728729203
antimicrobial susceptibility pattern of clinical isolates of burkholderia pseudomallei in bangladesh.melioidosis an infectious disease, caused by a gram negative bacterium called burkholderia pseudomallei, is endemic in bangladesh. this organism is sensitive to limited number of antimicrobial agents and need prolonged treatment. there is no comprehensive data on the antimicrobial susceptibility profile of b. pseudomallei isolated in bangladesh over last several years. the present study aimed to determine the antimicrobial susceptibility pattern of b. pseudomallei isolated in a tertiary care hos ...201728728591
susceptibility of clinical isolates of burkholderia pseudomallei to a lipid a biosynthesis inhibitor.burkholderia pseudomallei is the causative agent of melioidosis, a serious infection associated with high mortality and relapse. current antimicrobial therapy using ceftazidime (caz) is often ineffective. inhibitors of lpxc, the enzyme responsible for lipid a biosynthesis, have potential antimicrobial activity against several gram-negative bacteria in vivo, but their activity against b. pseudomallei is unclear. herein, we investigated the susceptibility of b. pseudomallei clinical isolates to lp ...201728719324
differences in inflammation patterns induced by african and asian burkholderia pseudomallei isolates in mice.abstractburkholderia pseudomallei is the causative agent of melioidosis, an emerging tropical disease of high mortality. sub-saharan africa represents potential melioidosis "hotspots"; however, to date, only a few cases have been reported. here in, we compared the inflammatory patterns induced by a b. pseudomallei strain recently isolated from a fatal gabonese case with the thai reference strain b. pseudomallei-1026b and burkholderia thailandensis-e264. ex vivo, no differences were observed in t ...201728719265
designing probes for immunodiagnostics: structural insights into an epitope targeting burkholderia infections.structure-based epitope prediction drives the design of diagnostic peptidic probes to reveal specific antibodies elicited in response to infections. we previously identified a highly immunoreactive epitope from the peptidoglycan-associated lipoprotein (pal) antigen from burkholderia pseudomallei, which could also diagnose burkholderia cepacia infections. here, considering the high phylogenetic conservation within burkholderia species, we ask whether cross-reactivity can be reciprocally displayed ...201728707874
melioidosis: an emerging infection with fatal outcomes.according to the centers for disease control and prevention, from being nonendemic for melioidosis, india has now become endemic for the disease since 2012. until then, melioidosis cases were being reported sporadically from india. there have been isolated case reports from few states across the country for the past few years. most of the times, burkholderia pseudomallei may be misreported as pseudomonas species, especially in resource-poor laboratories. due to its varied clinical presentation, ...201728701847
bacterial bloodstream infections in a tertiary infectious diseases hospital in northern vietnam: aetiology, drug resistance, and treatment outcome.bloodstream infections (bsis) are associated with high morbidity and mortality worldwide. however their aetiology, antimicrobial susceptibilities and associated outcomes differ between developed and developing countries. systematic data from vietnam are scarce. here we present aetiologic data on bsi in adults admitted to a large tertiary referral hospital for infectious diseases in hanoi, vietnam.201728701159
infected abdominal aortic aneurysms treated with extra-anatomic prosthesis bypass in the retroperitoneum.infected abdominal aortic aneurysms (iaaas) are rare but life-threatening diseases. the purpose of the present study was to report our experience of extra-anatomic prosthesis bypass in the retroperitoneum as a treatment for iaaas.201728687504
caspase-6 mediates resistance against burkholderia pseudomallei infection and influences the expression of detrimental cytokines.caspase-6 is a member of the executioner caspases and known to play a role in innate and adaptive immune processes. however, its role in infectious diseases has rarely been addressed yet. we here examined the impact of caspase-6 in an in vivo infection model using the gram-negative rod burkholderia pseudomallei, causing the infectious disease melioidosis that is endemic in tropical and subtropical areas around the world. caspase-6-/- and c57bl/6 wild type mice were challenged with b. pseudomalle ...201728686630
gastrointestinal tract involvement in melioidosis.little is known about the involvement of the human gut in carriage and disease associated with burkholderia pseudomallei, the cause of melioidosis.201728673019
biochemical characterization and structural basis of reactivity and regioselectivity differences between burkholderia thailandensis and burkholderia glumae 1,6-didesmethyltoxoflavin n-methyltransferase.burkholderia glumae converts the guanine base of guanosine triphosphate into an azapteridine and methylates both the pyrimidine and triazine rings to make toxoflavin. strains of burkholderia thailandensis and burkholderia pseudomallei have a gene cluster encoding seven putative biosynthetic enzymes that resembles the toxoflavin gene cluster. four of the enzymes are similar in sequence to bgtoxbcde, which have been proposed to make 1,6-didesmethyltoxoflavin (1,6-ddmt). one of the remaining enzyme ...201728665591
type iii secretion in the melioidosis pathogen burkholderia pseudomallei.burkholderia pseudomallei is a gram-negative intracellular pathogen and the causative agent of melioidosis, a severe disease of both humans and animals. melioidosis is an emerging disease which is predicted to be vastly under-reported. type iii secretion systems (t3sss) are critical virulence factors in gram negative pathogens of plants and animals. the genome of b. pseudomallei encodes three t3sss. t3ss-1 and -2, of which little is known, are homologous to hrp2 secretion systems of the plant pa ...201728664152
genome-scale analysis of the genes that contribute to burkholderia pseudomallei biofilm formation identifies a crucial exopolysaccharide biosynthesis gene cluster.burkholderia pseudomallei, the causative agent of melioidosis, is an important public health threat due to limited therapeutic options for treatment. efforts to improve therapeutics for b. pseudomallei infections are dependent on the need to understand the role of b. pseudomallei biofilm formation and its contribution to antibiotic tolerance and persistence as these are bacterial traits that prevent effective therapy. in order to reveal the genes that regulate and/or contribute to b. pseudomalle ...201728658258
[homology analysis and historical tracing for inter-continental burkholderia pseudomallei strains of sequence type 562].objective: to understand the homology of sequence type 562 (st562) strains of burkholderia pseudomallei which circulated in two separate continents (asia and australia) at different times. methods:speⅰrestriction fragments and 4-locus multiple locus variable number tandem repeat analysis (mlva-4) profiles were extracted from mshr5858 (st562 australia strain) and 350105 (st562 historical strain of hainan) genomes respectively by in silico analysis and then compared with the pfge and mlva-4 result ...201728651407
development of a real-time loop-mediated isothermal amplification assay for detection of burkholderia mallei.burkholderia mallei is the aetiological agent of glanders, a highly contagious and re-emerging zoonotic disease. early diagnosis of glanders is critically important to ensure timely treatment with appropriate antibiotics in humans, and to prevent spread of infection in animals. molecular detection of b. mallei has always been troublesome because of its genetic similarity with burkholderia pseudomallei, the causative agent of melioidosis. in present investigation, a set of six b. mallei-specific ...201728649808
effects of sodium chloride on heat resistance, oxidative susceptibility, motility, biofilm and plaque formation of burkholderia pseudomallei.burkholderia pseudomallei is an environmental saprophyte and the causative agent of melioidosis, a severe infectious disease prevalent in tropical areas, including southeast asia and northern australia. in thailand, the highest incidence of melioidosis is in the northeast region, where saline soil and water are abundant. we hypothesized that b. pseudomallei develops an ability to thrive in saline conditions and gains a selective ecological advantage over other soil-dwelling microorganisms. howev ...201728643413
rapid filter-based detection and culture of burkholderia pseudomallei from small volumes of urine.clinical outcomes of melioidosis patients improve when the infecting agent, burkholderia pseudomallei, is rapidly detected and identified by laboratory testing. detection of b. pseudomallei dna or recovery of the pathogen by culture from urine can support a diagnosis of melioidosis and guide patient care. two new methods, designated filter-capture dna isolation (fcdi) and filter cellular recovery (fcr), were developed to increase the sensitivity of detection and recovery of viable b. pseudomalle ...201728637908
development of a multiplex pcr assay for the detection and differentiation of burkholderia pseudomallei, burkholderia mallei, burkholderia thailandensis, and burkholderia cepacia complex.two species of burkholderia pseudomallei complex (bpc), b. pseudomallei and b. mallei, can cause severe life-threatening infections. rapidly discerning individual species within the group and separating them from other opportunistic pathogens of the burkholderia cepacia complex (bcc) is essential to establish a correct diagnosis and for epidemiological surveillance. in this study, a multiplex pcr assay based on the detection of an individual set of chromosomal beta-lactamase genes for single-ste ...201728634144
host gene expression analysis in sri lankan melioidosis patients.melioidosis is a life threatening infectious disease caused by the gram-negative bacillus burkholderia pseudomallei predominantly found in southeast asia and northern australia. studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. the aim of this study was to analyze gene expression levels of human host factors in melioidosis patients an ...201728628607
phylogeography of burkholderia pseudomallei isolates, western hemisphere.the bacterium burkholderia pseudomallei causes melioidosis, which is mainly associated with tropical areas. we analyzed single-nucleotide polymorphisms (snps) among genome sequences from isolates of b. pseudomallei that originated in the western hemisphere by comparing them with genome sequences of isolates that originated in the eastern hemisphere. analysis indicated that isolates from the western hemisphere form a distinct clade, which supports the hypothesis that these isolates were derived f ...201728628442
pediatric melioidosis in sarawak, malaysia: epidemiological, clinical and microbiological characteristics.melioidosis is a serious, and potentially fatal community-acquired infection endemic to northern australia and southeast asia, including sarawak, malaysia. the disease, caused by the usually intrinsically aminoglycoside-resistant burkholderia pseudomallei, most commonly affects adults with predisposing risk factors. there are limited data on pediatric melioidosis in sarawak.201728599008
burkholderia pseudomallei in a lowland rice paddy: seasonal changes and influence of soil depth and physico-chemical properties.melioidosis, a severe infection with the environmental bacterium burkholderia pseudomallei, is being recognised increasingly frequently. what determines its uneven distribution within endemic areas is poorly understood. we cultured soil from a rice field in laos for b. pseudomallei at different depths on 4 occasions over a 13-month period. we also measured physical and chemical parameters in order to identify associated characteristics. overall, 195 of 653 samples (29.7%) yielded b. pseudomallei ...201728596557
an avirulent burkholderia pseudomallei ∆purm strain with atypical type b lps: expansion of the toolkit for biosafe studies of melioidosis.the work was undertaken to expand the tools available for researching burkholderia pseudomallei (bp), the etiological agent of the tropical disease melioidosis. melioidosis has the potential to pose a severe threat to public health and safety. in the united states, bp is listed as a tier-1 select agent by the centers for disease control and prevention (cdc), thus requiring high levels of regulation and biosafety level 3 (bsl3) facilities for experimental manipulation of live organisms. an avirul ...201728592242
hydrological connectivity and burkholderia pseudomallei prevalence in wetland environments: investigating rice-farming community's risk of exposure to melioidosis in north-east thailand.in our analysis of 136 water samples from wetland environments (rice paddies, natural wetland sites, man-made water bodies) in rural areas of north-east thailand, burkholderia pseudomallei was most prevalent in rice paddies (15 of the 30 positive sites). the high prevalence in the water of rice fields is indicative of the inherent vulnerability of farmers in rural agricultural areas in this area of thailand and likely other locations in the tropics. nearly all b. pseudomallei-positive sites were ...201728536911
improved detection of burkholderia pseudomallei from non-blood clinical specimens using enrichment culture and pcr: narrowing diagnostic gap in resource-constrained settings.to evaluate the diagnostic utility of enrichment culture and pcr for improved case detection rates of non-bacteraemic form of melioidosis in limited resource settings.201728510994
burkholderia thailandensis: genetic manipulation.burkholderia thailandensis is a gram-negative bacterium endemic to southeast asian and northern australian soils. it is non-pathogenic; therefore, it is commonly used as a model organism for the related human pathogens burkholderia mallei and burkholderia pseudomallei. b. thailandensis is relatively easily genetically manipulated and a variety of robust genetic tools can be used in this organism. this unit describes protocols for conjugation, natural transformation, mini-tn7 insertion, and allel ...201728510362
antibodies against in vivo-expressed antigens are sufficient to protect against lethal aerosol infection with burkholderia mallei and burkholderia pseudomallei.burkholderia mallei, a facultative intracellular bacterium and tier 1 biothreat, causes the fatal zoonotic disease glanders. the organism possesses multiple genes encoding autotransporter proteins, which represent important virulence factors and targets for developing countermeasures in pathogenic gram-negative bacteria. in the present study, we investigated one of these autotransporters, bata, and demonstrate that it displays lipolytic activity, aids in intracellular survival, is expressed in v ...201728507073
are brucellosis, q fever and melioidosis potential causes of febrile illness in madagascar?brucellosis, q fever and melioidosis are zoonoses, which can lead to pyrexia. these diseases are often under-ascertained and underreported because of their unspecific clinical signs and symptoms, insufficient awareness by physicians and public health officers and limited diagnostic capabilities, especially in low-resource countries. therefore, the presence of brucella spp., coxiella burnetii and burkholderia pseudomallei was investigated in malagasy patients exhibiting febrile illness. in additi ...201728502643
melioidosis: clinical impact and public health threat in the tropics.this review briefly summarizes the geographical distribution and clinical impact of melioidosis, especially in the tropics. burkholderia pseudomallei (a gram-negative bacterium) is the major causative agent for melioidosis, which is prevalent in singapore, malaysia, thailand, vietnam, and northern australia. melioidosis patients are increasingly being recognized in other parts of the world. the bacteria are intrinsically resistant to many antimicrobial agents, but prolonged treatment, especially ...201728493905
dna vaccination resurfaces in the struggle against melioidosis. 201728481716
a nonsense mutation in tlr5 is associated with survival and reduced il-10 and tnf-α levels in human melioidosis.melioidosis, caused by the flagellated bacterium burkholderia pseudomallei, is a life-threatening and increasingly recognized emerging disease. toll-like receptor (tlr) 5 is a germline-encoded pattern recognition receptor to bacterial flagellin. we evaluated the association of a nonsense tlr5 genetic variant that truncates the receptor with clinical outcomes and with immune responses in melioidosis.201728475641
melioidosis with portal vein thrombosis.melioidosis, caused by burkholderia pseudomallei, is a common infectious disease in tropical regions. the author reports a case of melioidosis with a rare manifestation of portal vein thrombosis and cavernous transformation of the portal vein. melioidosis should be considered a differential diagnosis in patients with underlying risk factors who present with multiple liver abscesses; moreover, portal vein thrombosis can be a potential complication. computed tomography is the modality of choice to ...201728473933
functional characterisation of burkholderia pseudomallei biotin protein ligase: a toolkit for anti-melioidosis drug development.burkholderia pseudomallei (bp) is the causative agent of melioidosis. the bacterium is responsible for 20% of community-acquired sepsis cases and 40% of sepsis-related mortalities in northeast thailand, and is intrinsically resistant to aminoglycosides, macrolides, rifamycins, cephalosporins, and nonureidopenicillins. there is no vaccine and its diagnosis is problematic. biotin protein ligase (bira) which is essential for fatty acid synthesis has been proposed as a drug target in bacteria. very ...201728454708
structural diversity of burkholderia pseudomallei lipopolysaccharides affects innate immune signaling.burkholderia pseudomallei (bp) causes the disease melioidosis. the main cause of mortality in this disease is septic shock triggered by the host responding to lipopolysaccharide (lps) components of the gram-negative outer membrane. bp lps is thought to be a weak inducer of the host immune system. lps from several strains of bp were purified and their ability to induce the inflammatory mediators tnf-α and inos in murine macrophages at low concentrations was investigated. innate and adaptive immun ...201728453531
central nervous system melioidosis in the pediatric age group: review.melioidosis is a potentially fatal infectious disease caused by burkholderia pseudomallei. neurologic involvement in pediatric age group is very rare, and only a handful of cases have been reported in literature. we sought to provide a systematic review of pediatric neurologic melioidosis.201728451778
demonstrating the protective efficacy of the novel fluoroquinolone finafloxacin against an inhalational exposure to burkholderia pseudomallei.burkholderia pseudomallei is the causative agent of melioidosis, a serious disease endemic in southeast asia and northern australia. antibiotic treatment is lengthy and relapse often occurs. finafloxacin is a novel fluoroquinolone with increased antibacterial activity in acidic conditions in contrast to other fluoroquinolones which demonstrate reduced activity at a lower ph. therefore, finafloxacin may have improved efficacy against b. pseudomallei, which can survive within host cells where the ...201728438936
gene expression profile of human cytokines in response to burkholderia pseudomallei infection.melioidosis is an underreported infectious disease, caused by the gram-negative bacterium burkholderia pseudomallei. understanding the disease susceptibility and pathogenesis is crucial for developing newer diagnostic and therapeutic strategies for this life-threatening infection. in this study, we aimed to analyze the gene expression levels of important cytokines in melioidosis patients and establish useful correlates with disease biomarkers compared to cases of sepsis infection caused by other ...201728435890
genomics reveals a unique clone of burkholderia cenocepacia harboring an actively excising novel genomic island.burkholderia cenocepacia is a clinically dominant form among the other virulent species of burkholderia cepacia complex (bcc). in the present study, we sequenced and analyzed the genomes of seven nosocomial bcc isolates, five of which were isolated from the bloodstream infections and two isolates were recovered from the hospital setting during the surveillance. genome-based species identification of the bcc isolates using a type strain explicitly identified the species as b. cenocepacia. moreove ...201728428775
the gut microbiota as a modulator of innate immunity during melioidosis.melioidosis, caused by the gram-negative bacterium burkholderia pseudomallei, is an emerging cause of pneumonia-derived sepsis in the tropics. the gut microbiota supports local mucosal immunity and is increasingly recognized as a protective mediator in host defenses against systemic infection. here, we aimed to characterize the composition and function of the intestinal microbiota during experimental melioidosis.201728422970
increased neurotropic threat from burkholderia pseudomallei strains with a b. mallei-like variation in the bima motility gene, australia.neurologic melioidosis is a serious, potentially fatal form of burkholderia pseudomallei infection. recently, we reported that a subset of clinical isolates of b. pseudomallei from australia have heightened virulence and potential for dissemination to the central nervous system. in this study, we demonstrate that this subset has a b. mallei-like sequence variation of the actin-based motility gene, bima. compared with b. pseudomallei isolates having typical bima alleles, isolates that contain the ...201728418830
acute bacteremic pneumonia due to melioidosis developing in the intensive care setting.in malaysia, melioidosis is commonly encountered as this infection is known as part of the endemic area for the disease. managing cases of positive burkholderia pseudomallei infection can involve multidisciplinary unit mainly, microbiologist, infectious disease team and intensive care as it may be quite difficult to distinguish melioidosis from a number of other diseases on the clinical setting alone. laboratory diagnosis plays a vital role in determining the direction of management. investigati ...201728417070
comparing in vitro and in vivo virulence phenotypes of burkholderia pseudomallei type g strains.burkholderia pseudomallei (bpm) is a saprophytic rod-shaped gram-negative bacterium and the causative agent of melioidosis. this disease has previously been described as endemic in areas such as northern australia and southeast asia, but, more recently, a better understanding of the epidemiology of melioidosis indicated that the disease is distributed worldwide, including regions of the americas and africa. a 16s-23s rdna internal transcribed spacer (its) typing system has been developed for bpm ...201728414823
accidental occupational exposure to burkholderia pseudomallei in south korea did not result in melioidosis. 201728414016
within-host evolution of burkholderia pseudomallei during chronic infection of seven australasian cystic fibrosis patients.cystic fibrosis (cf) is a genetic disorder characterized by progressive lung function decline. cf patients are at an increased risk of respiratory infections, including those by the environmental bacterium burkholderia pseudomallei, the causative agent of melioidosis. here, we compared the genomes of b. pseudomallei isolates collected between ~4 and 55 months apart from seven chronically infected cf patients. overall, the b. pseudomallei strains showed evolutionary patterns similar to those of o ...201728400528
preparing for biological threats: addressing the needs of pregnant women.intentional release of infectious agents and biological weapons to cause illness and death has the potential to greatly impact pregnant women and their fetuses. we review what is known about the maternal and fetal effects of seven biological threats: bacillus anthracis (anthrax); variola virus (smallpox); clostridium botulinum toxin (botulism); burkholderia mallei (glanders) and burkholderia pseudomallei (melioidosis); yersinia pestis (plague); francisella tularensis (tularemia); and rickettsia ...201728398677
antibiotic resistance markers in burkholderia pseudomallei strain bp1651 identified by genome sequence analysis.burkholderia pseudomallei bp1651 is resistant to several classes of antibiotics that are usually effective for treatment of melioidosis, including tetracyclines, sulfonamides, and β-lactams such as penicillins (amoxicillin-clavulanic acid), cephalosporins (ceftazidime), and carbapenems (imipenem and meropenem). we sequenced, assembled, and annotated the bp1651 genome and analyzed the sequence using comparative genomic analyses with susceptible strains, keyword searches of the annotation, publicl ...201728396541
microbial rhamnolipid production: a critical re-evaluation of published data and suggested future publication criteria.high production cost and potential pathogenicity of pseudomonas aeruginosa, commonly used for rhamnolipid synthesis, have led to extensive research for safer producing strains and cost-effective production methods. this has resulted in numerous research publications claiming new non-pathogenic producing strains and novel production techniques many of which are unfortunately without proper characterisation of product and/or producing strain/s. genes responsible for rhamnolipid production have onl ...201728386631
comparison of mast burkholderia cepacia, ashdown + gentamicin, and burkholderia pseudomallei selective agar for the selective growth of burkholderia spp.reliable identification of pathogenic burkholderia spp. like burkholderia mallei and burkholderia pseudomallei in clinical samples is desirable. three different selective media were assessed for reliability and selectivity with various burkholderia spp. and nontarget organisms. mast burkholderia cepacia agar, ashdown + gentamicin agar, and b. pseudomallei selective agar were compared. a panel of 116 reference strains and well-characterized clinical isolates, comprising 30 b. pseudomallei, 20 b. ...201728386468
whole-genome sequences of burkholderia pseudomallei isolates exhibiting decreased meropenem susceptibility.we report here paired isogenic burkholderia pseudomallei genomes obtained from three patients receiving intravenous meropenem for melioidosis treatment, with post-meropenem isolates developing decreased susceptibility. two genomes were finished, and four were drafted to improved high-quality standard. these genomes will be used to identify meropenem resistance mechanisms in b. pseudomallei.201728385830
matrix-assisted laser desorption/ionization time-of-flight mass spectrometry for the identification of burkholderia pseudomallei from asia and australia and differentiation between burkholderia species.matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (maldi-tof ms) is increasingly used for rapid bacterial identification. studies of burkholderia pseudomallei identification have involved small isolate numbers drawn from a restricted geographic region. there is a need to expand the reference database and evaluate b. pseudomallei from a wider geographic distribution that more fully captures the extensive genetic diversity of this species. here, we describe the evaluatio ...201728384252
biosynthesis of di-rhamnolipids and variations of congeners composition in genetically-engineered escherichia coli.to engineer escherichia coli for the heterologous production of di-rhamnolipids, which are important biosurfactants but mainly produced by opportunistic pathogen pseudomonas aeruginosa.201728374071
comparison of o-polysaccharide and hemolysin co-regulated protein as target antigens for serodiagnosis of melioidosis.melioidosis is a severe disease caused by burkholderia pseudomallei. clinical manifestations are diverse and acute infections require immediate treatment with effective antibiotics. while culture is the current diagnostic standard, it is time-consuming and has low sensitivity. in endemic areas, inaccessibility to biosafety level 3 facilities and a lack of good serodiagnostic tools can impede diagnosis and disease surveillance. recent studies have suggested that o-polysaccharide (ops) and hemolys ...201728358816
neuromelioidosis: a series of seven cases in hainan province, china.melioidosis, which is caused by burkholderia pseudomallei, is predominately a disease of tropical climates and is especially widespread in south-east asia and northern australia. melioidosis affecting the central nervous system has a low incidence but a high mortality. we present seven cases of neuromelioidosis and analyze the disease characteristics and imaging features. typical clinical features of this disease included high fever and headache. five patients had an irregular fever with a tempe ...201728351287
whole-genome sequencing of a quarter-century melioidosis outbreak in temperate australia uncovers a region of low-prevalence endemicity.melioidosis, caused by the highly recombinogenic bacterium burkholderia pseudomallei, is a disease with high mortality. tracing the origin of melioidosis outbreaks and understanding how the bacterium spreads and persists in the environment are essential to protecting public and veterinary health and reducing mortality associated with outbreaks. we used whole-genome sequencing to compare isolates from a historical quarter-century outbreak that occurred between 1966 and 1991 in the avon valley, we ...201628348862
loss of methyltransferase function and increased efflux activity leads to doxycycline resistance in burkholderia pseudomallei.the soil-dwelling bacterium burkholderia pseudomallei is the causative agent of the potentially fatal disease melioidosis. the lack of a vaccine towards b. pseudomallei means that melioidosis treatment relies on prolonged antibiotic therapy, which can last up to six months in duration or longer. due to intrinsic resistance, few antibiotics are effective against b. pseudomallei the lengthy treatment regimen required increases the likelihood of resistance development, with subsequent potentially f ...201728348161
burkholderia pseudomallei and burkholderia mallei vaccines: are we close to clinical trials?b. pseudomallei is the cause of melioidosis, a serious an often fatal disease of humans and animals. the closely related bacterium b. mallei, which cases glanders, is considered to be a clonal derivative of b. pseudomallei. both b. pseudomallei and b. mallei were evaluated by the united states and the former ussr as potential bioweapons. much of the effort to devise biodefence vaccines in the past decade has been directed towards the identification and formulation of sub-unit vaccines which coul ...201728336210
rapid dna vaccination against burkholderia pseudomallei flagellin by tattoo or intranasal application.melioidosis is a severe infectious disease with a high mortality that is endemic in south-east asia and northern australia. the causative pathogen, burkholderia pseudomallei, is listed as potential bioterror weapon due to its high virulence and potential for easy dissemination. currently, there is no licensed vaccine for prevention of melioidosis. here, we explore the use of rapid plasmid dna vaccination against b. pseudomallei flagellin for protection against respiratory challenge. we tested th ...201728323523
a proteasome inhibitor produced by burkholderia pseudomallei modulates intracellular growth.the nrps/pks cluster encodes the enzymes necessary for glidobactin synthesis it is partially conserved in various members of the burkholderia genus including b. pseudomallei. in this study we have shown that the insertional inactivation or deletion of glbc in this cluster in b. pseudomallei could reduce the ability of the bacterium to survive or grow in murine macrophages or in human neutrophils. exogenously added proteasome inhibitors were able to chemically complement the mutation. the inserti ...201728323151
increased von willebrand factor, decreased adamts13 and thrombocytopenia in melioidosis.melioidosis, caused by bioterror treat agent burkholderia pseudomallei, is an important cause of community-acquired gram-negative sepsis in southeast asia and northern australia. new insights into the pathogenesis of melioidosis may help improve treatment and decrease mortality rates from this dreadful disease. we hypothesized that changes in von willebrand factor (vwf) function should occur in melioidosis, based on the presence of endothelial stimulation by endotoxin, pro-inflammatory cytokines ...201728296884
molecular architecture of the n-type atpase rotor ring from burkholderia pseudomallei.the genome of the highly infectious bacterium burkholderia pseudomallei harbors an atp operon that encodes an n-type rotary atpase, in addition to an operon for a regular f-type rotary atpase. the molecular architecture of n-type atpases is unknown and their biochemical properties and cellular functions are largely unexplored. we studied the b. pseudomallei n1no-type atpase and investigated the structure and ion specificity of its membrane-embedded c-ring rotor by single-particle electron cryo-m ...201728283532
general assay for enzymes in the heptose biosynthesis pathways using electrospray ionization mass spectrometry.the adp-l-glycero-β-d-manno-heptose and the gdp-6-deoxy-α-d-manno-heptose biosynthesis pathways play important roles in constructing lipopolysaccharide of gram-negative bacteria. blocking the pathways is lethal or increases antibiotic susceptibility to pathogens. therefore, the enzymes involved in the pathways are novel antibiotic drug targets. here, we designed an efficient method to assay the whole enzymes in the pathways using mass spectrometry and screened 148 compounds. one promising lead i ...201728280867
complete genome sequence of a burkholderia pseudomallei strain isolated from a pet green iguana in prague, czech republic.burkholderia pseudomallei was isolated from pus from an abscess of a pet iguana living in a private household in prague, czech republic. this paper presents the complete genome sequence of b. pseudomallei strain vb976100.201728280033
comparison of the sulfonamide inhibition profiles of the β- and γ-carbonic anhydrases from the pathogenic bacterium burkholderia pseudomallei.we have cloned, purified, and characterized a β-carbonic anhydrase (ca, ec 4.2.1.1), bpscaβ, from the pathogenic bacterium burkholderia pseudomallei, responsible for the tropical disease melioidosis. the enzyme showed high catalytic activity for the physiologic co₂ hydration reaction to bicarbonate and protons, with the following kinetic parameters: kcat of 1.6 × 10⁵ s(-1) and kcat/km of 3.4 × 10⁷ m(-1) s(-1). an inhibition study with a panel of 38 sulfonamides and one sulfamate-including 15 com ...201728272358
the expanding role of type ii secretion in bacterial pathogenesis and beyond.type ii secretion (t2s) is one means by which gram-negative pathogens secrete proteins into the extracellular milieu and/or host organisms. based upon recent genome sequencing, it is clear that t2s is largely restricted to the proteobacteria, occurring in many, but not all genera in the α-, β-, γ-, and δ- classes. prominent human and/or animal pathogens that express a t2s system(s) include acinetobacter baumannii, burkholderia pseudomallei, chlamydia trachomatis, escherichia coli, klebsiella pne ...201728264910
comparison of the anion inhibition profiles of the β- and γ-carbonic anhydrases from the pathogenic bacterium burkholderia pseudomallei.we report the cloning, purification and characterization of bpsβca, a β-class carbonic anhydrase (ca, ec 4.2.1.1) from the pathogenic bacterium burkholderia pseudomallei, the etiological agent of melioidosis, and compare its activity and inhibition with those of the γ-ca from the same organism, bpsγca, recently investigated by our groups. bpsβca showed a significant catalytic activity for the physiologic, co2 hydration reaction, with the following kinetic parameters, kcat of 1.6×10(5)s(-1) and k ...201728238511
[chronic skin ulcer in a 24-year-old man after a journey to southeast asia].our report concerns a 24-year-old man with a chronic exsudative skin lesion after a journey to southeast asia. the diagnosis of melioidosis was made by the identification of burkholderia pseudomallei from the ichor. the diagnosis was confirmed by polymerase change reaction. the patient was treated with meropenem i. v. for about 10 days and with trimethoprim/sulfamethoxazole for the following 12 weeks. melioidosis is an endemic disease in southeast asia and north australia which in some cases can ...201728235984
characterization of pathogenesis of and immune response to burkholderia pseudomallei k96243 using both inhalational and intraperitoneal infection models in balb/c and c57bl/6 mice.burkholderia pseudomallei, the etiologic agent of melioidosis, is a gram negative bacterium designated as a tier 1 threat. this bacterium is known to be endemic in southeast asia and northern australia and can infect humans and animals by several routes. inhalational melioidosis has been associated with monsoonal rains in endemic areas and is also a significant concern in the biodefense community. there are currently no effective vaccines for b. pseudomallei and antibiotic treatment can be hampe ...201728235018
reply to "burkholderia pseudomallei: challenges for the clinical microbiology laboratory-a response from the front line". 201728232504
burkholderia pseudomallei: challenges for the clinical microbiology laboratory-a response from the front line. 201728232503
rationalizing the binding kinetics for the inhibition of the burkholderia pseudomallei fabi1 enoyl-acp reductase.there is growing awareness of the link between drug-target residence time and in vivo drug activity, and there are increasing efforts to determine the molecular factors that control the lifetime of a drug-target complex. rational alterations in the drug-target residence time require knowledge of both the ground and transition states on the inhibition reaction coordinate, and we have determined the structure-kinetic relationship for 22 ethyl- or hexyl-substituted diphenyl ethers that are slow-bin ...201728225601
interleukin 10 inhibits pro-inflammatory cytokine responses and killing of burkholderia pseudomallei.melioidosis, caused by burkholderia pseudomallei, is endemic in northeastern thailand and northern australia. severe septicemic melioidosis is associated with high levels of pro-inflammatory cytokines and is correlated with poor clinical outcomes. il-10 is an immunoregulatory cytokine, which in other infections can control the expression of pro-inflammatory cytokines, but its role in melioidosis has not been addressed. here, whole blood of healthy seropositive individuals (n = 75), living in n. ...201728216665
multitarget quantitative pcr improves detection and predicts cultivability of the pathogen burkholderia pseudomallei.burkholderia pseudomallei is present in the environment in many parts of the world and causes the often-fatal disease melioidosis. the sensitive detection and quantification of b. pseudomallei in the environment are a prerequisite for assessing the risk of infection. we recently reported the direct detection of b. pseudomallei in soil samples using a quantitative pcr (qpcr) targeting a single type three secretion system 1 (ttss1) gene. here, we extend the qpcr-based analysis of b. pseudomallei i ...201728188208
two stable variants of burkholderia pseudomallei strain mshr5848 express broadly divergent in vitro phenotypes associated with their virulence differences.burkholderia pseudomallei (bp), the agent of melioidosis, causes disease ranging from acute and rapidly fatal to protracted and chronic. bp is highly infectious by aerosol, can cause severe disease with nonspecific symptoms, and is naturally resistant to multiple antibiotics. however, no vaccine exists. unlike many bp strains, which exhibit random variability in traits such as colony morphology, bp strain mshr5848 exhibited two distinct and relatively stable colony morphologies on sheep blood ag ...201728187198
complement-activated vitronectin enhances the invasion of nonphagocytic cells by bacterial pathogens burkholderia and klebsiella.burkholderia pseudomallei is a serum-resistant gram-negative bacterium capable of causing disseminated infections with metastatic complications. however, its interaction with nonphagocytic cells is poorly understood. we observed that exposure of b. pseudomallei and the closely related yet avirulent b. thailandensis to human plasma increased epithelial cell invasion by >20 fold. enhanced invasion was primarily driven by a plasma factor, which required a functional complement cascade, but surprisi ...201728186697
calprotectin as a biomarker for melioidosis disease progression and management.melioidosis is a neglected tropical disease that is caused by the bacterium burkholderia pseudomallei and is underreported in many countries where the disease is endemic. a long and costly administration of antibiotics is needed to clear infections, and there is an unmet need for biomarkers to guide antibiotic treatment and increase the number of patients that complete therapy. we identified calprotectin as a lead biomarker of b. pseudomallei infections and examined correlations between this ser ...201728179407
expression and crystallographic studies of d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase from burkholderia pseudomallei.the gram-negative bacterium burkholderia pseudomallei is the causative agent of melioidosis. d-glycero-β-d-manno-heptose-1-phosphate adenylyltransferase (hldc) is the fourth enzyme of the adp-l-glycero-β-d-manno-heptose biosynthesis pathway, which produces an essential carbohydrate comprising the inner core of lipopolysaccharide. therefore, hldc is a potential target of antibiotics against melioidosis. in this study, hldc from b. pseudomallei has been cloned, expressed, purified and crystallized ...201728177319
activation of mapk/erk signaling by burkholderia pseudomallei cycle inhibiting factor (cif).cycle inhibiting factors (cifs) are virulence proteins secreted by the type iii secretion system of some gram-negative pathogenic bacteria including burkholderia pseudomallei. cif is known to function to deamidate nedd8, leading to inhibition of cullin e3 ubiquitin ligases (crl) and consequently induction of cell cycle arrest. here we show that cif can function as a potent activator of mapk/erk signaling without significant activation of other signaling pathways downstream of receptor tyrosine k ...201728166272
osteomyelitis of humerus and intramuscular abscess due to melioidosis.melioidosis is a clinically diverse disease caused by gram negative bacterium burkholderia pseudomallei. it is a potential bioterrorism agent. the high risk group includes the agricultural and construction workers whose contact with contaminated soil and water may expose them to bacteria. the clinical manifestations varies from asymptomatic infection to overwhelming sepsis. to diagnose melioidosis a high index of suspicion along with isolation and identification of the organism from the clinical ...201728166079
osteoarticular and soft-tissue melioidosis in malaysia: clinical characteristics and molecular typing of the causative agent.melioidosis involving bone, joints, and soft tissue is rare and reported usually following dissemination of disease from infection elsewhere in the body; to a lesser degree, it can also be reported as the primary manifestation of melioidosis.201728141587
erratum to: pediatric suppurative parotitis caused by burkholderia pseudomallei.[this corrects the article doi: 10.1186/s40409-016-0086-3.].201728138332
validation of a monoclonal antibody-based immunofluorescent assay to detect burkholderia pseudomallei in blood cultures.identification of burkholderia pseudomallei, the cause of melioidosis, using routine methods takes several days. use of a monoclonal antibody-based immunofluorescent assay (ifa) on positive blood cultures may speed diagnosis.201728115683
global and regional dissemination and evolution of burkholderia pseudomallei.the environmental bacterium burkholderia pseudomallei causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. we used whole genome sequences of 469 b. pseudomallei isolates from 30 countries collected over 79 years to explore its geographic transmission. our data point to australia as an early reservoir, with transmission to southeast asia followed by onward transmission to south asia and east asia. repeated reintroductions were obse ...201728112723
molecular tracking investigation of melioidosis cases reveals regional endemicity in hainan, china.sporadic cases of melioidosis have been reported in hainan, china for decades; however, to the best of our knowledge, there are no accurate source-identification investigations confirming that melioidosis is endemic. four indigenous melioidosis cases were identified, which prompted the performance of contact microbiologic and molecular techniques to evaluate endemicity. environmental samples were collected from various locations surrounding each patient's residence. the samples were screened for ...201628105344
causes and outcomes of sepsis in southeast asia: a multinational multicentre cross-sectional study.improved understanding of pathogens that cause sepsis would aid management and antimicrobial selection. in this study, we aimed to identify the causative pathogens of sepsis in southeast asia.201728104185
disseminated melioidosis in the head and neck.a 35-year-old man was admitted to an intensive care unit with unilateral facial swelling and septic shock after multiple presentations to the emergency department with non-specific unilateral pain over the parotid area. a ct scan of his neck showed diffuse right-sided facial soft tissue infection, mastoid effusion and temporal lobe cerebritis. the upper lobes of his lungs had cannonball lesions that were suggestive of septic lung metastases. blood cultures and ear canal swabs were positive for b ...201728096229
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