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 B. mallei-like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.
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 B. mallei-like variation demonstrate increased persistence in phagocytic cells and increased virulence with rapid systemic dissemination and replication within multiple tissues, including the brain and spinal cord, in an experimental model. These findings highlight the implications of bimA variation on disease progression of B. pseudomallei infection and have considerable clinical and public health implications with respect to the degree of neurotropic threat posed to human health.
Citation. Tumapa, S., Holden, M. T., Vesaratchavest, M., Wuthiekanun, V., Limmathurotsakul, D., Chierakul, W., Feil, E. J., Currie, B. J., Day, N. P., Nierman, W. C., Peacock, S. J.. Burkholderia pseudomallei Genome Plasticity Associated With Genomic Island Variation. BMC Genomics. 2008 Apr 25; 9(1): 190.. PubMed Citation. Abstract. ABSTRACT: BACKGROUND: Burkholderia pseudomallei is a soil-dwelling saprophyte and the cause of melioidosis. Horizontal gene transfer contributes to the genetic diversity of this pathogen and may be an important determinant of virulence potential. The genome contains genomic island (GI) regions that encode a broad array of functions. Although there is some evidence for the variable distribution of genomic islands in B. pseudomallei isolates, little is known about the extent of variation between related strains or their association with disease or environmental survival. RESULTS: Five islands from B. pseudomallei strain K96243 were chosen as representatives of ...
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 similar to 4 and 55 months apart from seven chronically infected CF patients. Overall, the B. pseudomallei strains showed evolutionary patterns similar to those of other chronic infections, including emergence of antibiotic resistance, genome reduction, and deleterious mutations in genes involved in virulence, metabolism, environmental survival, and cell wall components. We documented the first reported B. pseudomallei hypermutators, which were likely caused by defective MutS. Further, our study identified both known and novel molecular mechanisms conferring resistance to three of the five clinically important antibiotics for melioidosis treatment. Our ...
TY - JOUR. T1 - Malleilactone is a Burkholderia pseudomallei virulence factor regulated by antibiotics and quorum sensing. AU - Klaus, Jennifer R.. AU - Deay, Jacqueline. AU - Neuenswander, Benjamin. AU - Hursh, Wyatt. AU - Gao, Zhe. AU - Bouddhara, Tiffany. AU - Williams, Todd D.. AU - Douglas, Justin. AU - Monize, Kyle. AU - Martins, Patricia. AU - Majerczyk, Charlotte. AU - Seyedsayamdost, Mohammad R.. AU - Peterson, Blake R.. AU - Rivera, Mario. AU - Chandler, Josephine R.. PY - 2018/7/1. Y1 - 2018/7/1. N2 - Burkholderia pseudomallei, the causative agent of melioidosis, encodes almost a dozen predicted polyketide (PK) biosynthetic gene clusters. Many of these are regulated by LuxR-I-type acyl-homoserine (AHL) quorum-sensing systems. One of the PK gene clusters, the mal gene cluster, is conserved in the close relative Burkholderia thailandensis. The B. thailandensis mal genes code for the cytotoxin malleilactone and are regulated by a genetically linked LuxR-type transcription factor, MalR. ...
Melioidosis caused by the environmental gram-negative bacillus Burkholderia pseudomallei, is classically characterized by pneumonia and multiple abscesses, wit...
TY - JOUR. T1 - Epidemiological tracking and population assignment of the non-clonal bacterium, burkholderia pseudomallei. AU - Dale, Julia. AU - Price, Erin P.. AU - Hornstra, Heidie. AU - Busch, Joseph D.. AU - Mayo, Mark. AU - Godoy, Daniel. AU - Wuthiekanun, Vanaporn. AU - Baker, Anthony. AU - Foster, Jeffrey T. AU - Wagner, David M. AU - Tuanyok, Apichai. AU - Warner, Jeffrey. AU - Spratt, Brian G.. AU - Peacock, Sharon J.. AU - Currie, Bart J.. AU - Keim, Paul S. AU - Pearson, Talima R. PY - 2011/12. Y1 - 2011/12. N2 - Rapid assignment of bacterial pathogens into predefined populations is an important first step for epidemiological tracking. For clonal species, a single allele can theoretically define a population. For non-clonal species such as Burkholderia pseudomallei, however, shared allelic states between distantly related isolates make it more difficult to identify population defining characteristics. Two distinct B. pseudomallei populations have been previously identified using ...
Ceftazidime is the antibiotic of choice for treatment of Burkholderia pseudomallei infections (melioidosis). The chromosomally encoded PenA β-lactamase possesses weak cephalosporinase activity. The wild-type penA gene confers clinically significant ceftazidime resistance only when overexpressed due to a promoter mutation, transcriptional anti-termination or by gene duplication and amplification (GDA). Here we characterize a reversible 33-kb GDA event involving wild-type penA in a ceftazidime resistant clinical isolate from Thailand. We show that duplication arises from exchanges between short (|10 base pairs, bp) chromosomal sequences, which in this example consist of 4 bp repeats flanked by 3 bp inverted repeats. GDA involving β-lactamase may be a common ceftazidime resistance mechanism in B. pseudomallei.
Burkholderia pseudomallei, the etiological agent of melioidosis, is a saprophytic bacterium existing endemically in the water and soil of SE Asia and Northern Australia. This organism has shown the ability to remain dormant in its host for decades. B. thailandensis is a closely related non-pathogenic near neighbor that is also found in these soils. It has been suggested that free-living amoeba could be natural reservoirs for these organisms. The interactions of Burkholderia species and Acanthamoeba castellanii, a species of free-living amoeba, were studied to better understand the natural ecology of these organisms and to determine the effects amoeba interactions might have on pathogenesis. In this study, the adherence and persistence of several B. pseudomallei clinical isolates were compared to that of B. thailandensis within both amoeba and a human monocyte cell line. Results showed that B. pseudomallei isolates can enter amoeba and survive therein at varying levels of efficiency. Some isolates were
Our proteomic analysis of the B. pseudomallei MSHR668 T2SS secretome revealed the presence of ∼50 proteins dependent on the T2SS for export. Numerous hydrolytic enzymes, including 12 putative peptidases, were members of the T2SS secretome. Previous studies suggest that MprA, a serine metalloprotease, is responsible for the majority of protease activity in B. pseudomallei supernatants (39, 55, 56). However, the results presented here indicate that MprA is not the only protease exported by the B. pseudomallei T2SS (Table 2). Valade et al. constructed a mprA mutant and showed that a small amount of protease activity was still present in the supernatant when it was grown in rich medium, which is consistent with our results (56). Although MprA is likely responsible for most of the protease activity present in B. pseudomallei supernatants, we speculate that one or more of the T2SS-dependent peptidases shown in Table 2 also play a minor role in the hydrolysis of protein substrates. It is also worth ...
TY - JOUR. T1 - Burkholderia pseudomallei Antibodies in Individuals Living in Endemic Regions in Northeastern Brazil. AU - Rolim, D.B.. AU - Vilar, D.C.F.L.. AU - De Goes Cavalcanti, L.P.. AU - Freitas, C.L.B.N.. AU - Inglis, Tim. AU - Nobre Rodrigues, J.L.N.. AU - Nagao-Dias, A.T.. PY - 2011. Y1 - 2011. N2 - A seroepidemiological investigation was conducted among the population of two municipalities in Northeastern Brazil. Immunoglobulin M (IgM) and IgG antibodies to Burkholderia pseudomallei were positive in 51.27% (161 in 317 samples) and 58.49% (186), respectively. IgM titers were higher in children than in adults. On the contrary, IgG increased progressively with age. We observed a significant association between agricultural occupation and raised IgM titers (P ,0.005) and IgG titers (P ,0.001), and between construction workers and raised IgG titers (P = 0.005). Antibody IgG avidities did not correlate with age. The highest titers of antibodies (1/800) showed the highest antibody avidity ...
Easton A, Haque https://www.ncbi.nlm.nih.gov/pubmed/?term=19829050%5Bpmid%5DA, Chu K, Lukaszewski R, Bancroft GJ. 2007. A critical role for neutrophils in resistance to experimental infection with Burkholderia pseudomallei. J Infect Dis 195: 99-107. A Critical Role for Neutrophils in Resistance to Experimental Infection with Burkholderia pseudomallei. ...
Background Burkholderia pseudomallei is the causative agent of melioidosis, a disease of significant morbidity and mortality in both human and animals in endemic areas. There is no vaccine towards the bacterium available in the market, and the efficacy of many of the bacteriums surface and secreted proteins are currently being evaluated as vaccine candidates. Methodology/Principal Findings With the availability of the B. pseudomallei whole genome sequence, we undertook to identify genes encoding the known immunogenic outer membrane protein A (OmpA). Twelve OmpA domains were identified and ORFs containing these domains were fully annotated. Of the 12 ORFs, two of these OmpAs, Omp3 and Omp7, were successfully cloned, expressed as soluble protein and purified. Both proteins were recognised by antibodies in melioidosis patients sera by Western blot analysis. Purified soluble fractions of Omp3 and Omp7 were assessed for their ability to protect BALB/c mice against B. pseudomallei infection. Mice were
Burkholderia pseudomallei (also known as Pseudomonas pseudomallei) is a Gram-negative, bipolar, aerobic, motile rod-shaped bacterium. It is a soil-dwelling bacterium endemic in tropical and subtropical regions worldwide, particularly in Thailand and northern Australia. It infects humans and animals and causes the disease melioidosis. It is also capable of infecting plants. B. pseudomallei measures 2-5 μm in length and 0.4-0.8 μm in diameter and is capable of self-propulsion using flagella. The bacteria can grow in a number of artificial nutrient environments, especially betaine- and arginine-containing ones. In vitro, optimal proliferation temperature is reported around 40 °C in neutral or slightly acidic environments (pH 6.8-7.0). The majority of strains are capable of fermentation of sugars without gas formation (most importantly, glucose and galactose; older cultures are reported to also metabolize maltose and starch). Bacteria produce both exo- and endotoxins. The role of the toxins ...
Kynurenine formamidase (KynB) forms part of the kynurenine pathway which metabolises tryptophan to anthranilate. This metabolite can be used for downstream production of 2-alkyl-4-quinolone (AQ) signalling molecules that control virulence in Pseudomonas aeruginosa. Here we investigate the role of kynB in the production of AQs and virulence-associated phenotypes of Burkholderia pseudomallei K96243, the causative agent of melioidosis. Deletion of kynB resulted in reduced AQ production, increased biofilm formation, decreased swarming and increased tolerance to ciprofloxacin. Addition of exogenous anthranilic acid restored the biofilm phenotype, but not the persister phenotype. This study suggests the kynurenine pathway is a critical source of anthranilate and signalling molecules that may regulate B. pseudomallei virulence ...
Burkholderia pseudomallei is the causative agent of melioidosis, a fatal human tropical disease. The non-specific DNA-binding protein DpsA plays a key role in protecting B. pseudomallei from oxidative stress mediated, for example, by organic hydroperoxides. The regulation of dpsA expression is poorly understood but one possibility is that it is regulated in a cell population density-dependent manner via N-acylhomoserine lactone (AHL)-dependent quorum sensing (QS) since a lux-box motif has been located within the dpsA promoter region. Using liquid chromatography and tandem mass spectrometry, it was first established that B. pseudomallei strain PP844 synthesizes AHLs. These were identified as N-octanoylhomoserine lactone (C8-HSL), N-(3-oxooctanoyl)homoserine lactone (3-oxo-C8-HSL), N-(3-hydroxyoctanoyl)-homoserine lactone (3-hydroxy-C8-HSL), N-decanoylhomoserine lactone (C10-HSL), N-(3-hydroxydecanoyl) homoserine lactone (3-hydroxy-C10-HSL) and N-(3-hydroxydodecanoyl)homoserine lactone (3-hydroxy-C12-HSL)
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Burkholderia pseudomallei is a Gram-negative bacterium that causes the serious human disease, melioidosis. There is no vaccine against melioidosis and it can be fatal if not treated with a specific antibiotic regimen, which typically includes the third-generation cephalosporin, ceftazidime (CAZ). There have been several resistance mechanisms described for B. pseudomallei, of which the best described are amino acid changes that alter substrate specificity in the highly conserved class A β-lactamase, PenA. In the current study, we sequenced penA from isolates sequentially derived from two melioidosis patients with wild-type (1.5 µg/mL) and, subsequently, resistant (16 or ≥256 µg/mL) CAZ phenotypes. We identified two single-nucleotide polymorphisms (SNPs) that directly increased CAZ hydrolysis. One SNP caused an amino acid substitution (C69Y) near the active site of PenA, whereas a second novel SNP was found within the penA promoter region. In both instances, the CAZ resistance phenotype ...
Burkholderia pseudomallei is the causative agent of the disease melioidosis, which is endemic in the tropics and a concern elsewhere as a biological warfare agent. Currently no human vaccine exists either in clinical trials or in a licensed form. Recently passively transferred monoclonal antibodies directed toward the expolysaccharide of B. pseudomallei have been shown to impart survival when administered prior to lethal challenge and active immunization using purified exopolysaccharide extends the mean time to death. Short peptides, termed mimotopes, mimicking native carbohydrate have been developed and used to induce protective responses against extracellular bacteria. Here the ability of mimotopes to generate a protective response against a pathogen that can invade host cells was investigated. Mimotopes immunoreactive to the passive protective monoclonals were developed and used to generate an antibody response against B. pseudomallei. Preliminary evaluation of the mimotopes in a murine ...
Burkholderia pseudomallei is a human and animal pathogen in tropical regions, especially Southeast Asia and northern Australia. Currently little is known about the genetics and molecular biology of this organism. In this report, we describe the mutagenesis of B. pseudomallei with the transposon Tn5-OT182. B. pseudomallei 1026b transposon mutants were obtained at a frequency of 4.6 x 10(-4) per initial donor cell, and the transposon inserted randomly into the chromosome. We used Tn5-OT182 to identify the flagellin structural gene, fliC. We screened 3,500 transposon mutants and identified 28 motility mutants. Tn5-OT182 integrated into 19 unique genetic loci encoding proteins with homology to Escherichia coli and Salmonella typhimurium flagellar and chemotaxis proteins. Two mutants, MM35 and MM36, contained Tn5-OT182 integrations in fliC. We cloned and sequenced fliC and used it to complement MM35 and MM36 in trans. The fliC transcriptional start site and a sigmaF-like promoter were identified by ...
Abstract 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 manifestations, however, is still unknown, in part because an effective method for LPS type identification is not available. Thus, we developed antigen capture immunoassays capable of distinguishing between the LPS types. Mice were injected with B or B2 LPS for atypical LPS-specific monoclonal antibody (mAb) isolation; only two mAbs (3A2 and 5B4) were isolated from mice immunized with B2 LPS. Immunoblot analysis and surface plasmon resonance demonstrated that 3A2 and 5B4 are reactive with both B2 and B LPS
Burkholderia pseudomallei is resistant to a diverse group of antimicrobials including third generation cephalosporins whilst quinolones and aminoglycosides have no reliable effect. As therapeutic options are limited, development of more effective forms of immunotherapy is vital to avoid a fatal outcome. In an earlier study, we reported on the B. pseudomallei serine MprA protease which is relatively stable over a wide pH and temperature range and digests physiological proteins. The present study was carried out to evaluate the immunogenicity and protective efficacy of the MprA as a potential vaccine candidate. In BALB/c mice immunized with recombinant MprA protease (smBpF4), a significantly high IgG titer was detectable. Isotyping studies revealed that the smBpF4-specific antibodies produced were predominantly IgG1, proposing that immunization with smBpF4 triggered a Th2 immune response. Mice were immunized with smBpF4 and subsequently challenged with B. pseudomallei via the intraperitoneal route. Whilst
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.,/p> ,p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.,/p> ,p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).,/p> ,p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x,sup>64,/sup> + x,sup>4,/sup> + x,sup>3,/sup> + x + 1. The algorithm is described in the ISO 3309 standard. ,/p> ,p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.,br /> ,strong>Cyclic redundancy and other checksums,/strong>,br /> ,a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993),/a>),/p> Checksum:i ...
Background 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. Methodology/Principal Findings Pathogenic species of Burkholderia contain an overabundance of TAAs, some of which have been shown to elicit an immune response in the host. To understand the structural basis for host cell adhesion, we solved a 1.35 Å resolution crystal structure of a BpaA TAA head domain from Burkholderia pseudomallei, the pathogen that causes melioidosis. The structure reveals a novel fold of an intricately intertwined trimer. The BpaA head is composed of structural elements that have been observed in other TAA head
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 avirulent ∆purM derivative of strain 1026b (Bp82) has proven to be a valuable tool for biosafe research as a select-agent excluded strain, but the high level of genetic diversity between Bp strains necessitates an expansion of the biosafe toolset. The ∆purM mutation was recapitulated in the Bp 576a strain, a serotype B background. An important difference between strains 1026b and 576a is the lipopolysaccharide (LPS), a major virulence factor and protective antigen. Polyclonal sera from 1026b-challenged non-human
We evaluated the correlation of Burkholderia pseudomallei quantities in blood versus urine, sputum or pus. Correlations between bacterial counts in blood and other samples were not found. It is likely that an initial seeding event to extracellular organs is followed by independent growth of B. pseudomallei, and that bacteria in the urine were not passively filtered from the bloodstream.
Background: Although melioidosis in endemic regions is usually caused by a diverse range of Burkholderia pseudomallei strains, clonal outbreaks from contaminated potable water have been described. Furthermore B. pseudomallei is classified as a CDC Group B bioterrorism agent. Ribotyping, pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) have been used to identify genetically related B. pseudomallei isolates, but they are time consuming and technically challenging for many laboratories ...
Burkholderia pseudomallei is a gram-negative soil bacterium that is able to infect both humans and animals. Although cellculture based studies have revealed si...
The reaction of the catalase-peroxidase of Burkholderia pseudomallei with peroxyacetic acid has been analyzed using stopped-flow spectrophotometry. Two well-defined species were observed, the first de
Recently MALDI-TOF mass spectrum analysis has been considered an easy and discriminatory tool for identification of bacterial species (Lista et al., 2011). The results of MALDI-TOF mass spectrum analysis of the eight suspected isolates matched with that of the 16S rDNA sequence analysis. The four isolates DRDEBPS1001, DRDEBPS1002, DRDEBPS1003 and DRDEBPS1004 were confirmed as B. pseudomallei on the basis of score values 2.601, 2.099, 2.362 and 2.047. The other four isolates had been biochemically suspected but not supported by both the PCRs were also identified by MALDI-TOF spectrum analysis as Cupriavidus necator and Enterobacter cloacae with score value of 2.112, 2.122 and 2.341, 2.241 respectively, confirming the results of the 16S analysis.. The isolation of B. pseudomallei from soil is very complex as the presence of large numbers of closely related soil microflora interferes with its recovery although use of Ashdown broth and agar for the isolation of B. pseudomallei from soil samples ...
The overall goal of this project is to forensically characterize 100 unknown Burkholderia isolates in the US-Australia collaboration. We will identify genome-wide single nucleotide polymorphisms (SNPs) from B. pseudomallei and near neighbor species including B. mallei, B. thailandensis and B. oklahomensis. We will design microarray probes to detect these SNP markers and analyze 100 Burkholderia genomic DNAs extracted from environmental, clinical and near neighbor isolates from Australian collaborators on the Burkholderia SNP microarray. We will analyze the microarray genotyping results to characterize the genetic diversity of these new isolates and triage the samples for whole genome sequencing. In this interim report, we described the SNP analysis and the microarray probe design for the Burkholderia SNP microarray. ...
CUBRC, Inc. two weeks ago announced that CUBRCs Biological and Medical Sciences team, in collaboration with EpiVax, Inc., has received a four-year grant worth $1.87 million from the Defense Threat Reduction Agency (DTRA) within the Department of Defense (DoD). CUBRC, EpiVax, and scientists at the University of Florida will be investigating immune cells from patients that were previously infected with Burkholderiapseudomallei to understand how this bacterium evades the human immune system and use that information to engineer an effective vaccine. CUBRCs president and CEO, Tom McMahon, stated, "We are truly thankful for DTRAs confidence in our proposal to research vaccine antigens for prevention of Burkholderia pseudomallei infections, an important pathogen of biothreat potential.". CUBRC says it will leverage its technical expertise in biomedical R&D and its experience leading large federal government grants and contracts in collaboration with EpiVax and the University of Florida to execute ...
Burkholderia pseudomallei, the etiologic agent of melioidosis, is responsible for a broad spectrum of illnesses in humans and animals particularly in Southeast Asia and northern Australia, where it is endemic. Burkholderia thailandensisis a nonpathogenic environmental organism closely related to B. pseudomallei. Subtractive hybridization was carried out between these two species to identify genes encoding virulence determinants in B. pseudomallei. Screening of the subtraction library revealed A-T-rich DNA sequences unique toB. pseudomallei, suggesting they may have been acquired by horizontal transfer. One of the subtraction clones, pDD1015, encoded a protein with homology to a glycosyltransferase fromPseudomonas aeruginosa. This gene was insertionally inactivated in wild-type B. pseudomallei to create SR1015. It was determined by enzyme-linked immunosorbent assay and immunoelectron microscopy that the inactivated gene was involved in the production of a major surface polysaccharide. The 50% ...
Burkholderia pseudomallei is an intracellular pathogen and the causative agent of melioidosis, a life-threatening disease of humans. Within host cells, superoxide is an important mediator of pathogen killing. In this study, we have identified the B. pseudomallei K96243 sodC gene, shown that it has superoxide dismutase activity, and constructed an allelic deletion mutant of this gene. Compared with the wild-type, the mutant was more sensitive to killing by extracellular superoxide, but not to superoxide generated intracellularly. The sodC mutant showed a markedly decreased survival in J774A.1 mouse macrophages, and reduced numbers of bacteria were recovered from human polymorphonuclear neutrophils (PMNs) when compared with the wild-type. The numbers of wild-type or mutant bacteria recovered from human diabetic neutrophils were significantly lower than from normal human neutrophils. The sodC mutant was attenuated in BALB/c mice. Our results indicate that SodC plays a key role in the virulence of B.
Bossé, J. T., Li, Y., Angen, O., Weinert, L. A., Chaudhuri, R. R., Holden, M. T., Williamson, S. M., Maskell, D. J., Tucker, A. W., Wren, B. W., Rycroft, A. N., Langford, P. R., on behalf of the BRaDP1T consortium & Holden, M. Jul 2014 In : Journal of Clinical Microbiology. p. 2380-2385 6 p.. Research output: Contribution to journal › Article ...
2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). Contributed by Jeff F. Miller, July 13, 2019 (sent for review April 15, 2019; reviewed by Yunn-Hwen Gan and John J. Mekalanos). We thank the members of the J.F.M. laboratory for valuable discussions. We thank undergraduate researchers Minna Ding, Christy Kim, and Anh Huynh (UCLA) for their technical assistance. P.L.B. thanks Steve Smale, Kelsey Martin, Robert Modlin, Marcus Horwitz, Alex Hoffmann, Kent Hill, Ann Hirsch, Elizabeth Neufeld, Atish Ganguly, and Umesh Ahuja for their mentorship. We thank Bart Currie and his group at the Menzies School of Health Research for providing the MSHR305 Bp strain. We thank Romney Humphries and the UCLA Clinical Microbiology Laboratory for providing P. aeruginosa and E. coli strains. We also thank Colin Manoil (University of Washington) for providing us with the Bt transposon mutant library. ...
Ubiquinone (UQ), also called coenzyme Q, and plastoquinone (PQ) are electron carriers in oxidative phosphorylation and photosynthesis, respectively. The quinoid nucleus of ubiquinone is derived from the shikimate pathway; 4-hydroxybenzoate is directly formed from chorismate in bacteria, while it can be formed from either chorismate or tyrosine in yeast. The following biosynthesis of terpenoid moiety involves reactions of prenylation, decarboxylation, and three hydroxylations alternating with three methylations. The order of these reactions are somewhat different between bacteria and yeast. Phylloquinone (vitamin K1), menaquinone (vitamin K2), and tocopherol (vitamin E) are fat-soluble vitamins. Phylloquinone is a compound present in all photosynthetic plants serving as a cofactor for photosystem I-mediated electron transport. Menaquinone is an obligatory component of the electron-transfer pathway in bacteria ...
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adenylate kinase (Adk):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. We present here the three-dimensional protein structure of Burkholderia pseudomallei Adk. This pathogen is an aerobic, Gram-negative, soil-dwelling bacterium responsible for the infectious disease melioidosis, which is a serious health problem in Northern Australia and Southeast Asia and accounts for 40% of all sepsis-related mortality in northeast Thailand. Due to its potential use in biological warfare and biological terrorism, B. pseudomallei is also of concern to the U.S. Centers for Disease Control and Prevention. An unexpected feature of the BpAdk crystal structure was the observation of two significantly different conformations of the protein
Development and validation of |i|Burkholderia pseudomallei|/i|-specific real-time PCR assays for clinical, environmental or forensic detection applications
Lowe, W., J.K. March, A.J. Bunnell, K.L. ONeill, and R.A. Robison. 2013. PCR-based methodologies used to detect and differentiate the Burkholderia pseudomallei complex: B. pseudomallei, B. mallei, and B. thailandensis. Current Issues in Molecular Biology 16: 23-54.. Gunnell, M.K., Adams, B.J., and Robison, R.A. 2015. The genetic diversity and evolution of Francisella tularensis with comments on detection by PCR. Current Issues in Molecular Biology. 18: 79-92.. Gunnell, M.K., Robison, R.A., and Adams, B.J. 2016. Natural selection in virulence genes of Francisella tularensis. Journal of Molecular Evolution. DOI 10.1007/s00239-016-9743-y, 1-15.. Lowe, C-W, Satterfield, B.A., Nelson, D.B., Thiriot, J.D., Heder, M.J., March, J.K., Drake, D.S., Lew, C.S., Bunnell, A.J., Moore, E.S., ONeill, K.L., and Robison, R.A. 2016. A quaduplex real-time assay for the rapid detection and differentiation of the most relevant members of the B. pseudomallei complex: B. mallei, B. pseudomallei, and B. thailandensis. ...
Based on these results, we conclude Selleck Ro 61-8048 that BoaA is a well-conserved gene product shared by B. mallei and B. pseudomallei. Table 2 Percent identity shared by boaA and boaB gene products BoaA (Bm ATCC23344) BoaA (Bm NCTC10247) BoaA (Bp K96243) BoaA (Bp DD503) BoaA (Bp 1710b) BoaB (Bp K96243) BoaB (Bp DD503) BoaB (Bp 1710b) BoaA (Bm ATCC23344) 100 BoaA (Bm NCTC10247) 86.9 100 BoaA (Bp K96243) 92.7 89.2 100 BoaA (Bp DD503) 94.4 82.2 90.6 100 BoaA (Bp 1710b) 90.4 83.1 92.4 93.6 100 BoaB (Bp K96243) 64 60 65 63.9 63.9 100 BoaB (Bp. DD503) 62 60.8 62.9 61.9 62.2 96.7 100 BoaB (Bp 1710b) 62.2 60.9 63.2 62.1 62.4 97 99.7 100 Bm = B. mallei Bp = B. pseudomallei Identification of a B. pseudomallei-specific gene encoding a putative autotransporter adhesin that resembles BoaA Further analysis of the annotated genomic sequence of B. pseudomallei K96243 identified the ORF locus tag number BPSL1705 as specifying a second Oca-like protein that is ~60% identical to BoaA. The last 776 aa of ...
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ID DDL_BURP0 Reviewed; 312 AA. AC A3NZL3; DT 10-JUN-2008, integrated into UniProtKB/Swiss-Prot. DT 03-APR-2007, sequence version 1. DT 22-NOV-2017, entry version 75. DE RecName: Full=D-alanine--D-alanine ligase {ECO:0000255,HAMAP-Rule:MF_00047}; DE EC=6.3.2.4 {ECO:0000255,HAMAP-Rule:MF_00047}; DE AltName: Full=D-Ala-D-Ala ligase {ECO:0000255,HAMAP-Rule:MF_00047}; DE AltName: Full=D-alanylalanine synthetase {ECO:0000255,HAMAP-Rule:MF_00047}; GN Name=ddl {ECO:0000255,HAMAP-Rule:MF_00047}; GN OrderedLocusNames=BURPS1106A_3548; OS Burkholderia pseudomallei (strain 1106a). OC Bacteria; Proteobacteria; Betaproteobacteria; Burkholderiales; OC Burkholderiaceae; Burkholderia; pseudomallei group. OX NCBI_TaxID=357348; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=1106a; RA DeShazer D., Woods D.E., Nierman W.C.; RL Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Cell wall formation. {ECO:0000255,HAMAP-Rule:MF_00047}. CC -!- CATALYTIC ACTIVITY: ATP + 2 ...
Use this form (H3) for serodiagnosis of staphylococcal, streptococcal, Pseudomonas aeruginosa and Burkholderia pseudomallei antibodies.
Respiratory infections pose a threat to the health of the population worldwide. Within the RTG 1870 "Bacterial Respiratory Infections - Common and Specific Mechanisms of Pathogen Adaptation and Immune Defence" (BacRes) scientists of the University Greifswald carry out research projects on three versatile respiratory pathogens: Streptococcus pneumoniae (pneumococci), Staphylococcus aureus and Burkholderia pseudomallei. The bacteria can harmlessly colonize the nasopharynx, but also cause serious respiratory and invasive infections whose therapy poses huge problems, not least because of frequent antibiotic resistance of these pathogens. A better understanding of the potential of these bacteria to adapt to different environments in the human host and to evade the immune defense is urgently needed in order to develop novel therapeutic strategies and effective vaccines. This requires interdisciplinary research approaches and state-of-the-art experimental methods. Scientists of the UMG from infection ...
How can you expect a diabetic patient presented with mild fever and cough, very stable, able to walk, make jokes, laugh... like a mild infection, to end up in ICU and died within a day. I remember that patient was diagnosed as pneumonia based on symptoms and chest X-ray finding. Just mild perihilar hazziness. Admitted and started on Augmentin. A day after that, patient desaturate, intubated and was sent to ICU. That patient died after 1 day in ICU. 3 days later, blood cultures result came out to be Burkholderia pseudomallei. Its too late ...
Despite the pilgrims low bone signs of leprosy, the researchers were able to isolate M. leprae DNA from him for analysis. They first screened all three skeletons for signs of M. leprae using the multi-copy element RLEP, which they then confirmed by real-time PCR analysis of the multi-copy element IS1081. Only the pilgrim came back positive for M. leprae. The samples were also screened to determine whether they were infected with Brucella, Treponema pallidum, Burkholderia pseudomallei, Leishmania, Plasmodium, or hepatitis B virus, but none were. ...
The primary PhyloTrac window displays a taxonomic tree of the OTUs detected by the PhyloChip microarray, with mean intensities for each detected OTU displayed as a heat map of samples at the leaves of the tree. The user may dynamically filter the tree to hide low-abundance or borderline OTUs below user-specified intensity or PF thresholds, search and filter by keyword or clade, or summarize the analysis at any level of the tree from phylum to species. In Fig. 1a, the tree has been filtered to display the abundance of 19 select pathogenic or near-neighbor OTUs in San Antonio throughout the 17 weeks. In accordance with reference 2, the regular presence of phylogenetic near-neighbors to Bacillus anthracis, Burkholderia pseudomallei, and Clostridium botulinum is evident. In a second synchronized window, these OTUs are displayed in a time series plot, displaying their change in abundance over time, highlighted in yellow, in relation to all other OTUs, colored blue, and showing a spike in abundance in ...