Publications

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transient in vivo resistance mechanisms of burkholderia pseudomallei to ceftazidime and molecular markers for monitoring treatment response.much is known about the mode of action of drugs and resistance mechanisms under laboratory growth conditions, but research on the bacterial transcriptional response to drug pressure in vivo or efficacious mode of action and transient resistance mechanisms of clinically employed drugs is limited. accordingly, to assess active alternative metabolism and transient resistance mechanisms, and identify molecular markers of treatment response, the in vivo transcriptional response of burkholderia pseudo ...201728081127
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
erratum to: pediatric suppurative parotitis caused by burkholderia pseudomallei.[this corrects the article doi: 10.1186/s40409-016-0086-3.].201728138332
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
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
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
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
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
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
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
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
[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
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
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
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
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
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
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
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
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
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
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
development of immunoassays for burkholderia pseudomallei typical and atypical lipopolysaccharide strain typing.burkholderia pseudomallei is the causative agent of melioidosis, a severe infection endemic to many tropical regions. lipopolysaccharide (lps) is recognized as an important virulence factor used by b. pseudomallei isolates of b. pseudomallei have been shown to express one of four different types of lps (typical lps, atypical lps types b and b2, and rough lps) and in vitro studies have demonstrated that lps types may impact disease severity. the association between lps types and clinical manifest ...201727994103
characterization of in vitro phenotypes of burkholderia pseudomallei and burkholderia mallei strains potentially associated with persistent infection in mice.burkholderia pseudomallei (bp) and burkholderia mallei (bm), the agents of melioidosis and glanders, respectively, are tier 1 biothreats. they infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. first, a phenotyping strategy was developed employing colon ...201727738703
imported case of melioidosis in oman: case report.melioidosis is an infectious disease caused by the bacterium burkholderia pseudomallei. it is most commonly described in southeast asia and northern australia and some imported cases in non-endemic areas. we describe the case of a 55-year-old omani man with fulminant sepsis who worked in laos, cambodia. b. pseudomallei was isolated from the patient's blood and was identified by means of microbiological and biochemical tests. we highlight the importance of careful attention to non-fermentative gr ...201728042405
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
secondary metabolites from bacillus amyloliquefaciens isolated from soil can kill burkholderia pseudomallei.bacillus species are gram-positive bacteria found in abundance in nature and their secondary metabolites were found to possess various potential activities, notably antimicrobial. in this study, bacillus amyloliquefaciens n2-4 and n3-8 were isolated from soil and their metabolites could kill burkholderia pseudomallei, a gram-negative pathogenic bacterium also found in soil in its endemic areas. moreover, the metabolites were able to kill drug resistant isolates of b. pseudomallei and also inhibi ...201728050857
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