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burkholderia cenocepacia shvr-regulated genes that influence colony morphology, biofilm formation, and virulence.burkholderia cenocepacia is an opportunistic pathogen that primarily infects cystic fibrosis (cf) patients. previously, we reported that shvr, a lysr regulator, influences colony morphology, virulence, and biofilm formation and regulates the expression of an adjacent 24-kb genomic region encoding 24 genes. in this study, we report the functional characterization of selected genes in this region. a tn5 mutant with shiny colony morphology was identified with a polar mutation in bcas0208, predicted ...201121690240
the antibacterial properties of docosahexaenoic omega-3 fatty acid against the cystic fibrosis multi-resistant pathogen burkholderia cenocepacia.burkholderia cepacia complex (bcc) bacteria are opportunistic pathogens that cause multiresistant pulmonary infections in cystic fibrosis (cf) patients. in this study we evaluated the in vitro antimicrobial efficacy of eight unsaturated fatty acids against burkholderia cenocepacia k56-2, a cf epidemic strain. docosahexaenoic acid (dha) was the most active compound. its action can be either bacteriostatic or bactericidal, depending upon the concentration used. the effect of dha was also evaluated ...201122150831
host evasion by burkholderia cenocepacia.burkholderia cenocepacia is an opportunistic respiratory pathogen of individuals with cystic fibrosis (cf). some strains of b. cenocepacia are highly transmissible and resistant to almost all antibiotics. approximately one-third of b. cenocepacia infected cf patients go on to develop fatal "cepacia syndrome." during the last two decades, substantial progress has been made with regards to evasion of host innate defense mechanisms by b. cenocepacia. almost all strains of b. cenocepacia have the ca ...201122919590
can early burkholderia cepacia complex infection in cystic fibrosis be eradicated with antibiotic therapy?organisms of the burkholderia cepacia complex (bcc) are important pathogens in cystic fibrosis (cf). the majority of those who acquire bcc develop chronic infection but it can also result in rapid decline in a significant minority. in addition, chronic infection with burkholderia cenocepacia in particular is regarded as a contraindication to lung transplantation in many units. whilst aggressive antibiotic therapy is employed in cf to eradicate pseudomonas aeruginosa before infection becomes irre ...201122919584
genomic expression analysis reveals strategies of burkholderia cenocepacia to adapt to cystic fibrosis patients' airways and antimicrobial therapy.pulmonary colonization of cystic fibrosis (cf) patients with burkholderia cenocepacia or other bacteria of the burkholderia cepacia complex (bcc) is associated with worse prognosis and increased risk of death. during colonization, the bacteria may evolve under the stressing selection pressures exerted in the cf lung, in particular, those resulting from challenges of the host immune defenses, antimicrobial therapy, nutrient availability and oxygen limitation. understanding the adaptive mechanisms ...201122216120
3-hydroxyphenylacetic acid induces the burkholderia cenocepacia phenylacetic acid degradation pathway - toward understanding the contribution of aromatic catabolism to pathogenesis.the phenylacetic acid (pa) degradative pathway is the central pathway by which various aromatic compounds (e.g., styrene) are degraded. upper pathways for different aromatic compounds converge at common intermediate phenylacetyl-coa (pa-coa), which is then metabolized to succinyl-coa and acetyl-coa. we previously made a link in burkholderia cenocepacia between pa degradation and virulence by showing that insertional mutagenesis of paaa and paae genes, that encode part of a multicomponent oxidase ...201122919580
long-term colonization of the cystic fibrosis lung by burkholderia cepacia complex bacteria: epidemiology, clonal variation, and genome-wide expression alterations.long-term respiratory infections with burkholderia cepacia complex (bcc) bacteria in cystic fibrosis (cf) patients generally lead to a more rapid decline in lung function and, in some cases, to a fatal necrotizing pneumonia known as the "cepacia syndrome." bcc bacteria are ubiquitous in the environment and are recognized as serious opportunistic pathogens that are virtually impossible to eradicate from the cf lung, posing a serious clinical threat. the epidemiological survey of bcc bacteria invo ...201122919578
hopanoid production is required for low-ph tolerance, antimicrobial resistance, and motility in burkholderia cenocepacia.hopanoids are pentacyclic triterpenoids that are thought to be bacterial surrogates for eukaryotic sterols, such as cholesterol, acting to stabilize membranes and to regulate their fluidity and permeability. to date, very few studies have evaluated the role of hopanoids in bacterial physiology. the synthesis of hopanoids depends on the enzyme squalene-hopene cyclase (shc), which converts the linear squalene into the basic hopene structure. deletion of the 2 genes encoding shc enzymes in burkhold ...201121965564
burkholderia cenocepacia differential gene expression during host-pathogen interactions and adaptation to the host environment.members of the burkholderia cepacia complex (bcc) are important in medical, biotechnological, and agricultural disciplines. these bacteria naturally occur in soil and water environments and have adapted to survive in association with plants and animals including humans. all bcc species are opportunistic pathogens including burkholderia cenocepacia that causes infections in cystic fibrosis and chronic granulomatous disease patients. the adaptation of b. cenocepacia to the host environment was ass ...201122919581
a two-tier model of polymyxin b resistance in burkholderia cenocepacia.burkholderia cenocepacia is an environmental bacterium causing serious human opportunistic infections and is extremely resistant to multiple antibiotics including antimicrobial peptides, such as polymyxin b (pmb). extreme antibiotic resistance is attributed to outer membrane impermeability ('intrinsic' resistance). previous work showed that production of full-length lipopolysaccharide (lps) prevents surface binding of pmb. we hypothesized that two tiers of resistance mechanisms rendering differe ...201123761261
pcr detection of burkholderia cepacia complex as one of key factors to handle a long-term outbreak.once the outbreak with burkholderia cenocepacia st32 was identified in the prague cystic fibrosis (cf) centre, molecular tools were implemented into diagnostic routine in order to complement infection control measures with as accurate as possible microbiological service. in addition, genotyping techniques were applied as part of an infection surveillance program to assign species and strain status in samples positive for burkholderia cepacia complex (bcc). we sought to evaluate a usefulness of b ...201222622026
rhodococcus sp. strain cr-53 lipr, the first member of a new bacterial lipase family (family x) displaying an unusual y-type oxyanion hole, similar to the candida antarctica lipase clan.bacterial lipases constitute the most important group of biocatalysts for synthetic organic chemistry. accordingly, there is substantial interest in developing new valuable lipases. considering the lack of information concerning the lipases of the genus rhodococcus and taking into account the interest raised by the enzymes produced by actinomycetes, a search for putative lipase-encoding genes from rhodococcus sp. strain cr-53 was performed. we isolated, cloned, purified, and characterized lipr, ...201222226953
[mutants of burkholderia cenocepacia with a change in synthesis of n-acyl-homoserine lactones--signal molecules of quorum sensing regulation].by means of plasposon mutagenesis, mutants of burkholderia cenocepacia 370 with the change in production of n-acyl-homoserine lactones (ahl), signal molecules of the quorum sensing system of regulation, were obtained. to localize plasposon insertions in mutant strains, fragments of chromosomal dna containing plasposons were cloned, adjacent dna regions sequenced, and a search for homologous nucleotide sequences in the genebank was initiated. it has been shown that the insertion of plasposon into ...201222830256
successful treatment of cepacia syndrome with a combination of intravenous cyclosporin, antibiotics and oral corticosteroids.burkholderia cepacia complex (bcc) is a group of 17 closely related bacterial species that can cause pulmonary infection in patients with cystic fibrosis (cf). the clinical manifestations of bcc infection are varied but can include cepacia syndrome, which is a rapidly progressing necrotising pneumonia with an almost universally fatal outcome. we report the case of a 38 year old man, known to have chronic infection with the et12 strain of burkholderia cenocepacia who developed cepacia syndrome 26 ...201222551926
occurrence and antibiotic susceptibility profiles of burkholderia cepacia complex in coastal marine environment.during an environmental study of bacterial resistance to antibiotics in coastal waters of the kaštela bay, adriatic sea, croatia, 47 burkholderia cepacia complex (bcc) isolates were recovered from seawater and mussel (mytilus galloprovincialis) samples. all isolates showed multiple antibiotic resistance. among the isolates, two burkholderia cenocepacia isolates produced chromosomally encoded tem-116 extended-spectrum β-lactamase (esbl). analysis of outer membrane proteins revealed that decreased ...201222428949
inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide.biofilms cause up to 80% of infections and are difficult to treat due to their substantial multidrug resistance compared to their planktonic counterparts. based on the observation that human peptide ll-37 is able to block biofilm formation at concentrations below its mic, we screened for small peptides with antibiofilm activity and identified novel synthetic cationic peptide 1037 of only 9 amino acids in length. peptide 1037 had very weak antimicrobial activity, but at 1/30th the mic the peptide ...201222354291
interaction of environmental burkholderia cenocepacia strains with cystic fibrosis and non-cystic fibrosis bronchial epithelial cells in vitro.burkholderia cenocepacia is an important human pathogen in patients with cystic fibrosis (cf). non-clinical reservoirs may play a role in the acquisition of infection, so it is important to evaluate the pathogenic potential of environmental b. cenocepacia isolates. in this study, we investigated the interactions of two environmental b. cenocepacia strains (mex1 and mcii-168) with two bronchial epithelial cell lines, 16hbe14o(-) and cfbe41o(-), which have a non-cf and a cf phenotype, respectively ...201222322958
quorum sensing systems influence burkholderia cenocepacia virulence.burkholderia cepacia complex strains communicate using n-acyl homoserine lactones and bdsf-dependent quorum sensing (qs) systems. burkholderia cenocepacia qs systems include cepir, cciir, cepr2 and bdsf. analysis of cepr, cciir, cepr2 and rpff (bdsf synthase) qs regulons revealed that these qs systems both independently regulate and coregulate many target genes, often in an opposing manner. the role of qs and several qs-regulated genes in virulence has been determined using vertebrate, invertebr ...201223231487
aminoarabinose is essential for lipopolysaccharide export and intrinsic antimicrobial peptide resistance in burkholderia cenocepacia(†).one common mechanism of resistance against antimicrobial peptides in gram-negative bacteria is the addition of 4-amino-4-deoxy-l-arabinose (l-ara4n) to the lipopolysaccharide (lps) molecule. burkholderia cenocepacia exhibits extraordinary intrinsic resistance to antimicrobial peptides and other antibiotics. we have previously discovered that unlike other bacteria, b. cenocepacia requires l-ara4n for viability. here, we describe the isolation of b. cenocepacia suppressor mutants that remain viabl ...201222742453
the suhb gene of burkholderia cenocepacia is required for protein secretion, biofilm formation, motility and polymyxin b resistance.burkholderia cenocepacia is a member of the burkholderia cepacia complex (bcc), a group of gram-negative opportunistic pathogens that cause severe lung infections in patients with cystic fibrosis and display extreme intrinsic resistance to antibiotics, including antimicrobial peptides. b. cenocepacia bcal2157 encodes a protein homologous to suhb, an inositol-1-monophosphatase from escherichia coli, which was suggested to participate in post-transcriptional control of gene expression. in this wor ...201222767545
extracellular glutathione decreases the ability of burkholderia cenocepacia to penetrate into epithelial cells and to induce an inflammatory response.the airway surface liquid (asl) of cystic fibrosis (cf) patients contains a lower concentration of reduced glutathione (gsh) with respect to healthy people. it is not known whether this defect may favor lung colonization by opportunistic pathogens.201223094061
burkholderia cenocepacia lectin a binding to heptoses from the bacterial lipopolysaccharide.bacteria from the burkholderia cepacia complex (bcc) cause highly contagious pneumonia among cystic fibrosis (cf) patients. among them, burkholderia cenocepacia is one of the most dangerous in the bcc and is the most frequent cause of morbidity and mortality in cf patients. indeed, it is responsible of "cepacia syndrome", a deadly exacerbation of infection, that is the main cause of poor outcomes in lung transplantation. burkholderia cenocepacia produces several soluble lectins with specificity ...201222763039
synthesis and evaluation of the quorum sensing inhibitory effect of substituted triazolyldihydrofuranones.acylhomoserine lactone (ahl) analogues in which the amide function is replaced by a triazole group were synthesized and evaluated for their effect on quorum sensing (qs) and biofilm formation in burkholderia cenocepacia and pseudomonas aeruginosa. in addition, the influence of the length of the acyl-mimicking chain was investigated. the compounds showed selectivity between two different ahl qs systems. 3-(1h-1,2,3-triazol-1-yl)dihydrofuran-2(3h)-ones, in which the 4-substituent best resembled th ...201222748377
modelling co-infection of the cystic fibrosis lung by pseudomonas aeruginosa and burkholderia cenocepacia reveals influences on biofilm formation and host response.the gram-negative bacteria pseudomonas aeruginosa and burkholderia cenocepacia are opportunistic human pathogens that are responsible for severe nosocomial infections in immunocompromised patients and those suffering from cystic fibrosis (cf). these two bacteria have been shown to form biofilms in the airways of cf patients that make such infections more difficult to treat. only recently have scientists begun to appreciate the complicated interplay between microorganisms during polymicrobial inf ...201223284990
the ahl- and bdsf-dependent quorum sensing systems control specific and overlapping sets of genes in burkholderia cenocepacia h111.quorum sensing in burkholderia cenocepacia h111 involves two signalling systems that depend on different signal molecules, namely n-acyl homoserine lactones (ahls) and the diffusible signal factor cis-2-dodecenoic acid (bdsf). previous studies have shown that ahls and bdsf control similar phenotypic traits, including biofilm formation, proteolytic activity and pathogenicity. in this study we mapped the bdsf stimulon by rna-seq and shotgun proteomics analysis. we demonstrate that a set of the ide ...201223185499
a luxr-type repressor of burkholderia cenocepacia inhibits transcription via antiactivation and is inactivated by its cognate acylhomoserine lactone.burkholderia cenocepacia is an opportunistic human pathogen that encodes two luxi-type acylhomoserine lactone (ahl) synthases and three luxr-type ahl receptors. of these, cepi and cepr form a cognate synthase/receptor pair, as do ccii and ccir, while cepr2 lacks a genetically linked ahl synthase gene. another group showed that a cepr2 mutant overexpressed a cluster of linked genes that appear to direct the production of a secondary metabolite. we found that these same genes were upregulated by o ...201223136852
burkholderia cenocepacia bacteremia without respiratory colonization in an adult intensive care unit: epidemiological and molecular investigation of an outbreak.to investigate an outbreak of burkholderia cenocepacia bacteremia. observational study and chart review in a multidisciplinary adult intensive care unit (icu) at a tertiary care hospital.201223935310
burkholderia cenocepacia type vi secretion system mediates escape of type ii secreted proteins into the cytoplasm of infected macrophages.burkholderia cenocepacia is an opportunistic pathogen that survives intracellularly in macrophages and causes serious respiratory infections in patients with cystic fibrosis. we have previously shown that bacterial survival occurs in bacteria-containing membrane vacuoles (bccvs) resembling arrested autophagosomes. intracellular bacteria stimulate il-1β secretion in a caspase-1-dependent manner and induce dramatic changes to the actin cytoskeleton and the assembly of the nadph oxidase complex ont ...201222848580
a bcam0223 mutant of burkholderia cenocepacia is deficient in hemagglutination, serum resistance, adhesion to epithelial cells and virulence.burkholderia cepacia complex (bcc) bacteria are a problematic group of microorganisms causing severe infections in patients with cystic fibrosis. in early stages of infection, bcc bacteria must be able to adhere to and colonize the respiratory epithelium. although this is not fully understood, this primary stage of infection is believed to be in part mediated by a specific type of adhesins, named trimeric autotransporter adhesins (taas). these homotrimeric proteins exist on the surface of many g ...201222848588
high confidence prediction of essential genes in burkholderia cenocepacia.essential genes are absolutely required for the survival of an organism. the identification of essential genes, besides being one of the most fundamental questions in biology, is also of interest for the emerging science of synthetic biology and for the development of novel antimicrobials. new antimicrobial therapies are desperately needed to treat multidrug-resistant pathogens, such as members of the burkholderia cepacia complex.201222768221
identification of functions linking quorum sensing with biofilm formation in burkholderia cenocepacia h111.burkholderia cenocepacia has emerged as an important pathogen for patients suffering from cystic fibrosis (cf). previous work has shown that this organism employs the cepir quorum-sensing (qs) system to control the expression of virulence factors as well as the formation of biofilms. to date, however, very little is known about the qs-regulated virulence factors and virtually nothing about the factors that link qs and biofilm formation. here, we have employed a combined transcriptomic and proteo ...201222950027
a unique regulator contributes to quorum sensing and virulence in burkholderia cenocepacia.burkholderia cenocepacia causes chronic and life-threatening respiratory infections in immunocompromized people. the b. cenocepacia n-acyl-homoserine lactone (ahl)-dependent quorum sensing system relies on the production of ahls by the synthases cepi and ccii while cepr, ccir and cepr2 control expression of many genes important for pathogenesis. downstream from, and co-transcribed with cepi, lies bcam1871 encoding a hypothetical protein that was uncharacterized prior to this study. orthologs of ...201222624054
the use of nanoscale visible light-responsive photocatalyst tio2-pt for the elimination of soil-borne pathogens.exposure to the soil-borne pathogens burkholderia pseudomallei and burkholderia cenocepacia can lead to severe infections and even mortality. these pathogens exhibit a high resistance to antibiotic treatments. in addition, no licensed vaccine is currently available. a nanoscale platinum-containing titania photocatalyst (tio(2)-pt) has been shown to have a superior visible light-responsive photocatalytic ability to degrade chemical contaminants like nitrogen oxides. the antibacterial activity of ...201222384003
genome-scale ncrna homology search using a hamming distance-based filtration strategy.ncrnas (noncoding rnas) play important roles in many biological processes. existing genome-scale ncrna search tools identify ncrnas in local sequence alignments generated by conventional sequence comparison methods. however, some types of ncrna lack strong sequence conservation and tend to be missed or mis-aligned by conventional sequence comparison.201222536896
cis-2-dodecenoic acid receptor rpfr links quorum-sensing signal perception with regulation of virulence through cyclic dimeric guanosine monophosphate turnover.many bacterial pathogens produce diffusible signal factor (dsf)-type quorum sensing (qs) signals in modulation of virulence and biofilm formation. previous work on xanthomonas campestris showed that the rpfc/rpfg two-component system is involved in sensing and responding to dsf signals, but little is known in other microorganisms. here we show that in burkholderia cenocepacia the dsf-family signal cis-2-dodecenoic acid (bdsf) negatively controls the intracellular cyclic dimeric guanosine monopho ...201222949660
global changes in gene expression by the opportunistic pathogen burkholderia cenocepacia in response to internalization by murine macrophages.burkholderia cenocepacia is an opportunistic pathogen causing life-threatening infections in patients with cystic fibrosis. the bacterium survives within macrophages by interfering with endocytic trafficking and delaying the maturation of the b. cenocepacia-containing phagosome. we hypothesize that b. cenocepacia undergoes changes in gene expression after internalization by macrophages, inducing genes involved in intracellular survival and host adaptation.201222321740
structural-functional studies of burkholderia cenocepacia d-glycero-β-d-manno-heptose 7-phosphate kinase (hlda) and characterization of inhibitors with antibiotic adjuvant and antivirulence properties.as an essential constituent of the outer membrane of gram-negative bacteria, lipopolysaccharide contributes significantly to virulence and antibiotic resistance. the lipopolysaccharide biosynthetic pathway therefore serves as a promising therapeutic target for antivirulence drugs and antibiotic adjuvants. here we report the structural-functional studies of d-glycero-β-d-manno-heptose 7-phosphate kinase (hlda), an absolutely conserved enzyme in this pathway, from burkholderia cenocepacia. hlda is ...201223256532
tangled bank of experimentally evolved burkholderia biofilms reflects selection during chronic infections.how diversity evolves and persists in biofilms is essential for understanding much of microbial life, including the uncertain dynamics of chronic infections. we developed a biofilm model enabling long-term selection for daily adherence to and dispersal from a plastic bead in a test tube. focusing on a pathogen of the cystic fibrosis lung, burkholderia cenocepacia, we sequenced clones and metagenomes to unravel the mutations and evolutionary forces responsible for adaptation and diversification o ...201223271804
exaggerated inflammatory responses mediated by burkholderia cenocepacia in human macrophages derived from cystic fibrosis patients.cystic fibrosis (cf) is accompanied with heightened inflammation worsened by drug resistant burkholderia cenocepacia. human cf macrophage responses to b. cenocepacia are poorly characterized and variable in the literature. therefore, we examined human macrophage responses to the epidemic b. cenocepacia j2315 strain in order to identify novel anti-inflammatory targets. peripheral blood monocyte derived macrophages were obtained from 23 cf and 27 non-cf donors. macrophages were infected with b. ce ...201222728038
the exopolysaccharide gene cluster bcam1330-bcam1341 is involved in burkholderia cenocepacia biofilm formation, and its expression is regulated by c-di-gmp and bcam1349.in burkholderia cenocepacia, the second messenger cyclic diguanosine monophosphate (c-di-gmp) has previously been shown to positively regulate biofilm formation and the expression of cellulose and type-i fimbriae genes through binding to the transcriptional regulator bcam1349. here, we provide evidence that cellulose and type-i fimbriae are not involved in b. cenocepacia biofilm formation in flow chambers, and we identify a novel bcam1349/c-di-gmp-regulated exopolysaccharide gene cluster which i ...201223281338
the genetic basis of cadmium resistance of burkholderia cenocepacia.burkholderia species are highly resistant to heavy metals (hms), yet their resistance mechanisms are largely unknown. in this study we screened 5000 mini-tn5 transposon insertion mutants of burkholderia cenocepacia h111 for loss of cadmium tolerance. of the four genes identified three affected outer membrane biogenesis and integrity or dna repair. the fourth gene, bcae0587, encoded a p1-type atpase belonging to the cada family of hm exporters. cada-deficient strains lost the ability to grow in t ...201223760902
comparative analysis of two phenotypically-similar but genomically-distinct burkholderia cenocepacia-specific bacteriophages.genomic analysis of bacteriophages infecting the burkholderia cepacia complex (bcc) is an important preliminary step in the development of a phage therapy protocol for these opportunistic pathogens. the objective of this study was to characterize kl1 (vb_bces_kl1) and ah2 (vb_bces_ah2), two novel burkholderia cenocepacia-specific siphoviruses isolated from environmental samples.201222676492
the novel cis-encoded small rna h2cr is a negative regulator of hfq2 in burkholderia cenocepacia.small non-coding regulatory rnas (srnas) post-transcriptionally affect multiple phenotypes in prokaryotes and eukaryotes, yet most of the underlying regulatory mechanisms and the nature of the target mrnas remain unclear. here we report the identification and functional analysis of the novel cis-encoded srna h2cr, from the human opportunistic pathogen burkholderia cenocepacia j2315. the srna was found to negatively regulate the hfq2 mrna, through binding to part of the 5'-utr region of the hfq2 ...201223082228
activation of the pyrin inflammasome by intracellular burkholderia cenocepacia.burkholderia cenocepacia is an opportunistic pathogen that causes chronic infection and induces progressive respiratory inflammation in cystic fibrosis patients. recognition of bacteria by mononuclear cells generally results in the activation of caspase-1 and processing of il-1β, a major proinflammatory cytokine. in this study, we report that human pyrin is required to detect intracellular b. cenocepacia leading to il-1β processing and release. this inflammatory response involves the host adapte ...201222368275
centromere binding and evolution of chromosomal partition systems in the burkholderiales.how split genomes arise and evolve in bacteria is poorly understood. since each replicon of such genomes encodes a specific partition (par) system, the evolution of par systems could shed light on their evolution. the cystic fibrosis pathogen burkholderia cenocepacia has three chromosomes (c1, c2, and c3) and one plasmid (pbc), whose compatibility depends on strictly specific interactions of the centromere sequences (pars) with their cognate binding proteins (parb). however, the par systems of b ...201222522899
expression of phenazine biosynthetic genes during the arbuscular mycorrhizal symbiosis of glomus intraradices.to explore the molecular mechanisms that prevail during the establishment of the arbuscular mycorrhiza symbiosis involving the genus glomus, we transcriptionally analysed spores of glomus intraradices be3 during early hyphal growth. among 458 transcripts initially identified as being expressed at presymbiotic stages, 20% of sequences had homology to previously characterized eukaryotic genes, 30% were homologous to fungal coding sequences, and 9% showed homology to previously characterized bacter ...201224031884
agrobacteria lacking ornithine lipids induce more rapid tumour formation.ornithine lipids (ols) are phosphorus-free membrane lipids that are widespread among gram-negative bacteria. their basic structure consists of a 3-hydroxy fatty acyl group attached in amide linkage to the α-amino group of ornithine and a second fatty acyl group ester-linked to the 3-hydroxy position of the first fatty acid. it has been shown that ols can be hydroxylated within the amide-linked fatty acyl moiety, the secondary fatty acyl moiety or within the ornithine moiety. these modifications ...201222958119
the burkholderia cenocepacia bdsf quorum sensing fatty acid is synthesized by a bifunctional crotonase homologue having both dehydratase and thioesterase activities.signal molecules of the diffusible signal factor (dsf) family have been shown recently to be involved in regulation of pathogenesis and biofilm formation in diverse gram-negative bacteria. dsf signals are reported to be active not only on their cognate bacteria, but also on unrelated bacteria and the pathogenic yeast, candida albicans. dsfs are monounsaturated fatty acids of medium chain length containing an unusual cis-2 double bond. although genetic analyses had identified genes involved in ds ...201222221091
identification of burkholderia cenocepacia strain h111 virulence factors using nonmammalian infection hosts.burkholderia cenocepacia h111, a strain isolated from a cystic fibrosis patient, has been shown to effectively kill the nematode caenorhabditis elegans. we used the c. elegans model of infection to screen a mini-tn5 mutant library of b. cenocepacia h111 for attenuated virulence. of the approximately 5,500 b. cenocepacia h111 random mini-tn5 insertion mutants that were screened, 22 showed attenuated virulence in c. elegans. except for the quorum-sensing regulator cepr, none of the mutated genes c ...201323090963
biochemical and functional studies on the burkholderia cepacia complex bcen gene, encoding a gdp-d-mannose 4,6-dehydratase.this work reports the biochemical and functional analysis of the burkholderia cenocepacia j2315 bcen gene, encoding a protein with gdp-d-mannose 4,6-dehydratase enzyme activity (e.c.4.2.1.47). data presented indicate that the protein is active when in the tetrameric form, catalyzing the conversion of gdp-d-mannose into gdp-4-keto-6-deoxy-d-mannose. this sugar nucleotide is the intermediary necessary for the biosynthesis of gdp-d-rhamnose, one of the sugar residues of cepacian, the major exopolys ...201323460819
antibacterial activity of a lectin-like burkholderia cenocepacia protein.bacteriocins of the llpa family have previously been characterized in the γ-proteobacteria pseudomonas and xanthomonas. these proteins are composed of two mmbl (monocot mannose-binding lectin) domains, a module predominantly and abundantly found in lectins from monocot plants. genes encoding four different types of llpa-like proteins were identified in genomes from strains belonging to the burkholderia cepacia complex (bcc) and the burkholderia pseudomallei group. a selected recombinant llpa-lik ...201323737242
genomic characterization of jg068, a novel virulent podovirus active against burkholderia cenocepacia.as is true for many other antibiotic-resistant gram-negative pathogens, members of the burkholderia cepacia complex (bcc) are currently being assessed for their susceptibility to phage therapy as an antimicrobial treatment. the objective of this study was to perform genomic and limited functional characterization of the novel bcc phage jg068 (vb_bcep_jg068).201323978260
the many uses of autophagosomes.autophagy has emerged as a significant innate immune response to pathogens. typically, autophagosomes deliver their contents to lysosomes for degradation. some pathogens such as salmonella enterica serovar typhimurium succumb to autophagy and are transported to lysosomes for degradation. yet, many professional pathogens, including legionella pneumophila and burkholderia cenocepacia, subvert this pathway exploiting autophagy to their advantage.201323507956
immunoproteomic analysis of proteins expressed by two related pathogens, burkholderia multivorans and burkholderia cenocepacia, during human infection.burkholderia cepacia complex (bcc) is an opportunistic bacterial pathogen that causes chronic infections in people with cystic fibrosis (cf). it is a highly antibiotic resistant organism and bcc infections are rarely cleared from patients, once they are colonized. the two most clinically relevant species within bcc are burkholderia cenocepacia and burkholderia multivorans. the virulence of these pathogens has not been fully elucidated and the virulence proteins expressed during human infection h ...201324260482
burkholderia cenocepacia j2315 escapes to the cytosol and actively subverts autophagy in human macrophages.selective autophagy functions to specifically degrade cellular cargo tagged by ubiquitination, including bacteria. strains of the burkholderia cepacia complex (bcc) are opportunistic pathogens that cause life-threatening infections in patients with cystic fibrosis (cf) and chronic granulomatous disease (cgd). while there is evidence that defective macrophage autophagy in a mouse model of cf can influence b. cenocepacia susceptibility, there have been no comprehensive studies on how this bacteriu ...201324119232
discovery and characterization of a highly efficient enantioselective mandelonitrile hydrolase from burkholderia cenocepacia j2315 by phylogeny-based enzymatic substrate specificity prediction.a nitrilase-mediated pathway has significant advantages in the production of optically pure (r)-(-)-mandelic acid. however, unwanted byproduct, low enantioselectivity, and specific activity reduce its value in practical applications. an ideal nitrilase that can efficiently hydrolyze mandelonitrile to optically pure (r)-(-)-mandelic acid without the unwanted byproduct is needed.201323414071
cis-2-dodecenoic acid signal modulates virulence of pseudomonas aeruginosa through interference with quorum sensing systems and t3ss.cis-2-dodecenoic acid (bdsf) is well known for its important functions in intraspecies signaling in burkholderia cenocepacia. previous work has also established an important role of bdsf in interspecies and inter-kingdom communications. it was identified that bdsf modulates virulence of pseudomonas aeruginosa. however, how bdsf interferes with virulence of p. aeruginosa is still not clear.201324134835
antibacterial activity of eravacycline (tp-434), a novel fluorocycline, against hospital and community pathogens.eravacycline (tp-434 or 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline) is a novel fluorocycline that was evaluated for antimicrobial activity against panels of recently isolated aerobic and anaerobic gram-negative and gram-positive bacteria. eravacycline showed potent broad-spectrum activity against 90% of the isolates (mic90) in each panel at concentrations ranging from ≤0.008 to 2 μg/ml for all species panels except those of pseudomonas aeruginosa and burkholderia cenocepacia ...201323979750
structure of the chlamydia trachomatis immunodominant antigen pgp3.chlamydia trachomatis infection is the most common sexually transmitted bacterial disease. left untreated, it can lead to ectopic pregnancy, pelvic inflammatory disease, and infertility. here we present the structure of the secreted c. trachomatis protein pgp3, an immunodominant antigen and putative virulence factor. the ∼84-kda pgp3 homotrimer, encoded on a cryptic plasmid, consists of globular n- and c-terminal assemblies connected by a triple-helical coiled-coil. the c-terminal domains posses ...201323703617
proteomic profiling of burkholderia cenocepacia clonal isolates with different virulence potential retrieved from a cystic fibrosis patient during chronic lung infection.respiratory infections with burkholderia cepacia complex (bcc) bacteria in cystic fibrosis (cf) are associated with a worse prognosis and increased risk of death. in this work, we assessed the virulence potential of three b. cenocepacia clonal isolates obtained from a cf patient between the onset of infection (isolate ist439) and before death with cepacia syndrome 3.5 years later (isolate ist4113 followed by ist4134), based on their ability to invade epithelial cells and compromise epithelial mo ...201324349432
isolation and characterization of burkholderia rinojensis sp. nov., a non-burkholderia cepacia complex soil bacterium with insecticidal and miticidal activities.isolate a396, a bacterium isolated from a japanese soil sample demonstrated strong insecticidal and miticidal activities in laboratory bioassays. the isolate was characterized through biochemical methods, fatty acid methyl ester (fame) analysis, sequencing of 16s rrna, multilocus sequence typing and analysis, and dna-dna hybridization. fame analysis matched a396 to burkholderia cenocepacia, but this result was not confirmed by 16s rrna or dna-dna hybridization. 16s rrna sequencing indicated clos ...201324096416
draft genome sequences of burkholderia cenocepacia et12 lineage strains k56-2 and bc7.the burkholderia cepacia complex (bcc) is a group of closely related bacteria that are responsible for respiratory infections in immunocompromised humans, most notably those with cystic fibrosis (cf). we report the genome sequences for burkholderia cenocepacia et12 lineage cf isolates k56-2 and bc7.201324136849
identification and characterization of ϕh111-1: a novel myovirus with broad activity against clinical isolates of burkholderia cenocepacia.characterization of prophages in sequenced bacterial genomes is important for virulence assessment, evolutionary analysis, and phage application development. the objective of this study was to identify complete, inducible prophages in the cystic fibrosis (cf) clinical isolate burkholderia cenocepacia h111. using the prophage-finding program phage search tool (phast), we identified three putative intact prophages in the h111 sequence. virions were readily isolated from h111 culture supernatants f ...201324265978
characterization of the atsr hybrid sensor kinase phosphorelay pathway and identification of its response regulator in burkholderia cenocepacia.atsr is a membrane-bound hybrid sensor kinase of burkholderia cenocepacia that negatively regulates quorum sensing and virulence factors such as biofilm production, type 6-secretion, and protease secretion. here we elucidate the mechanism of atsr phosphorelay by site-directed mutagenesis of predicted histidine and aspartic acid phosphoacceptor residues. we demonstrate by in vitro phosphorylation that histidine 245 and aspartic acid 536 are conserved sites of phosphorylation in atsr, and we also ...201324014026
response of burkholderia cenocepacia h111 to micro-oxia.b. cenocepacia is an opportunistic human pathogen that is particularly problematic for patients suffering from cystic fibrosis (cf). in the cf lung bacteria grow to high densities within the viscous mucus that is limited in oxygen. pseudomonas aeruginosa, the dominant pathogen in cf patients, is known to grow and survive under oxygen-limited to anaerobic conditions by using micro-oxic respiration, denitrification and fermentative pathways. in contrast, inspection of the genome sequences of avail ...201324023794
mtvr is a global small noncoding regulatory rna in burkholderia cenocepacia.burkholderia cenocepacia j2315 is a highly epidemic and transmissible clinical isolate of the burkholderia cepacia complex (bcc), a group of bacteria causing life-threatening respiratory infections among cystic fibrosis patients. this work describes the functional analysis of the 136-nucleotide (nt)-long mtvr small noncoding rna (srna) from the bcc member b. cenocepacia j2315, with homologues restricted to the genus burkholderia. bioinformatic target predictions revealed a total of 309 mrnas to ...201323729649
snapbcen: a novel and practical tool for genotyping burkholderia cenocepacia.burkholderia cenocepacia is the most prevalent and feared member of the burkholderia cepacia complex in lung infections of cystic fibrosis (cf). genotyping and monitoring of long-term colonization are critical at clinical units; however, the differentiation of specific lineages performed by multilocus sequence typing (mlst) is still limited to a small number of isolates due to the high cost and time-consuming procedure. the aim of this study was to optimize a protocol (the snapbcen assay) for ex ...201323761147
cis-2-dodecenoic acid quorum sensing system modulates n-acyl homoserine lactone production through rpfr and cyclic di-gmp turnover in burkholderia cenocepacia.burkholderia cenocepacia employs both n-acyl homoserine lactone (ahl) and cis-2-dodecenoic acid (bdsf) quorum sensing (qs) systems in regulation of bacterial virulence. it was shown recently that disruption of bdsf synthase rpffbc caused a reduction of ahl signal production in b. cenocepacia. however, how bdsf system influences ahl system is still not clear.201323815566
structural stability of burkholderia cenocepacia biofilms is reliant on edna structure and presence of a bacterial nucleic acid binding protein.cystic fibrosis (cf) is the most common lethal inherited genetic disorder affection caucasians. even with medical advances, cf is life-shortening with patients typically surviving only to age 38. infection of the cf lung by burkholderia cenocepacia presents exceptional challenges to medical management of these patients as clinically this microbe is resistant to virtually all antibiotics, is highly transmissible and infection of cf patients with this microbe renders them ineligible for lung trans ...201323799151
the unexpected discovery of a novel low-oxygen-activated locus for the anoxic persistence of burkholderia cenocepacia.burkholderia cenocepacia is a gram-negative aerobic bacterium that belongs to a group of opportunistic pathogens displaying diverse environmental and pathogenic lifestyles. b. cenocepacia is known for its ability to cause lung infections in people with cystic fibrosis and it possesses a large 8 mb multireplicon genome encoding a wide array of pathogenicity and fitness genes. transcriptomic profiling across nine growth conditions was performed to identify the global gene expression changes made w ...201323486248
biofilm-grown burkholderia cepacia complex cells survive antibiotic treatment by avoiding production of reactive oxygen species.the presence of persister cells has been proposed as a factor in biofilm resilience. in the present study we investigated whether persister cells are present in burkholderia cepacia complex (bcc) biofilms, what the molecular basis of antimicrobial tolerance in bcc persisters is, and how persisters can be eradicated from bcc biofilms. after treatment of bcc biofilms with high concentrations of various antibiotics often a small subpopulation survived. to investigate the molecular mechanism of tole ...201323516582
burkholderia cenocepacia conditional growth mutant library created by random promoter replacement of essential genes.identification of essential genes by construction of conditional knockouts with inducible promoters allows the identification of essential genes and creation of conditional growth (cg) mutants that are then available as genetic tools for further studies. we used large-scale transposon delivery of the rhamnose-inducible promoter, prhab followed by robotic screening of rhamnose-dependent growth to construct a genomic library of 106 burkholderia cenocepacia cg mutants. transposon insertions were fo ...201323389959
phenotypic and genotypic characterisation of burkholderia cenocepacia j2315 mutants affected in homoserine lactone and diffusible signal factor-based quorum sensing systems suggests interplay between both types of systems.many putative virulence factors of burkholderia cenocepacia are controlled by various quorum sensing (qs) circuits. these qs systems either use n-acyl homoserine lactones (ahl) or cis-2-dodecenoic acid ("burkholderia diffusible signal factor", bdsf) as signalling molecules. previous work suggested that there is little cross-talk between both types of systems. we constructed mutants in b. cenocepacia strain j2315, in which genes encoding cepi (bcam1870), ccii (bcam0239a) and the bdsf synthase (bc ...201323383071
genetic diversity of burkholderia contaminans isolates from cystic fibrosis patients in argentina.a total of 120 burkholderia cepacia complex isolates collected during 2004-2010 from 66 patients in two cystic fibrosis reference centers in argentina were analyzed. burkholderia contaminans was the species most frequently recovered (57.6%), followed by burkholderia cenocepacia (15%), a species distribution not reported so far. the reca-pcr-based techniques applied to the b. contaminans isolates revealed that 85% of the population carried the reca-st-71 allele. our results showed the utility of ...201323135937
efficient production of (r)-(-)-mandelic acid in biphasic system by immobilized recombinant e. coli.the recombinant escherichia coli m15/bcj2315 which harbored a mandelonitrilase from burkholderia cenocepacia j2315 was immobilized via catecholic chitosan and functionalized with magnetism by iron oxide nanoparticles. the immobilized cells showed high activity recovery, enhanced stability and good operability in the enantioselective hydrolysis of mandelonitrile to (r)-(-)-mandelic acid. furthermore, the immobilized cells were reused up to 15 cycles without any activity loss in completely hydroly ...201323906842
efficacy of the biocide steri-7 against the common gram-negative bacterial pathogens (burkholderia cenocepacia, burkholderia gladioli, burkholderia multivorans, pseudomonas aeruginosa and stenotrophomonas maltophilia) associated with cystic fibrosis (cf). 201323888610
experimental identification of small non-coding regulatory rnas in the opportunistic human pathogen burkholderia cenocepacia j2315.small non-coding regulatory rnas (srnas) play important roles in regulating gene expression at the post-transcriptional level and often require the rna chaperone hfq. the human opportunistic pathogen burkholderia cenocepacia j2315 encodes two distinct rna chaperones, hfq and hfq2. the present work describes the experimental identification and validation of 24 srnas from b. cenocepacia j2315, based on the co-purification of srnas with the bacterium hfq protein, followed by conversion into cdna, c ...201323142676
burkholderia multivorans survival and trafficking within macrophages.cystic fibrosis (cf) patients are at great risk of opportunistic lung infection, particularly by members of the burkholderia cepacia complex (bcc). this group of bacteria can cause damage to the lung tissue of infected patients and are difficult to eradicate due to their high levels of antibiotic resistance. although the highly virulent burkholderia cenocepacia has been the focus of virulence research for the past decade, burkholderia multivorans is emerging as the most prevalent bcc species inf ...201323105020
influence of ligand presentation density on the molecular recognition of mannose-functionalised glyconanoparticles by bacterial lectin bc2l-a.polyvalent carbohydrate-protein interactions play a key role in bio- and pathological processes, including cell-cell communication and pathogen invasion. in order to study, control and manipulate these interactions gold nanoparticles have been employed as a 3d scaffold, presenting carbohydrate ligands in a multivalent fashion for use as high affinity binding partners and a model system for oligosaccharide presentation at biomacromolecular surfaces. in this study, the binding of a series of manno ...201323666402
bdsf inhibits candida albicans adherence to urinary catheters.cis-2-dodecenoic acid (bdsf) is a quorum-sensing signal molecule produced by the opportunistic pathogen burkholderia cenocepacia and suppresses germ tube formation of candida albicans. an in vitro model for biofilm formation evaluated the influence of bdsf on c. albicans. biofilm morphology was observed using scanning electron microscopy, cell adherence was determined using polystyrene plates and siliconized urinary catheters, and the levels of expression of genes involved in adhesion were deter ...201323948468
chemical communication of antibiotic resistance by a highly resistant subpopulation of bacterial cells.the overall antibiotic resistance of a bacterial population results from the combination of a wide range of susceptibilities displayed by subsets of bacterial cells. bacterial heteroresistance to antibiotics has been documented for several opportunistic gram-negative bacteria, but the mechanism of heteroresistance is unclear. we use burkholderia cenocepacia as a model opportunistic bacterium to investigate the implications of heterogeneity in the response to the antimicrobial peptide polymyxin b ...201323844246
single-molecule atomic force microscopy unravels the binding mechanism of a burkholderia cenocepacia trimeric autotransporter adhesin.trimeric autotransporter adhesins (taas) are bacterial surface proteins that fulfil important functions in pathogenic gram-negative bacteria. prominent examples of taas are found in burkholderia cepacia complex, a group of bacterial species causing severe infections in patients with cystic fibrosis. while there is strong evidence that burkholderia cenocepacia taas mediate adhesion, aggregation and colonization of the respiratory epithelium, we still know very little about the molecular mechanism ...201323796134
fluorescent labeling agents for quorum-sensing receptors (flaqs) in live cells.lighten up: a selective fluorescent-labeling agent for quorum sensing (flaqs) can be used for the visualization of the communication pathway of bacteria in live cells (see figure). this represents a new, operationally simple, fast, and inexpensive tool for the imaging of quorum-sensing receptors by using fluorescently labeled signaling-molecule analogues.201323765553
the in vivo extracellular life of facultative intracellular bacterial parasites: role in pathogenesis.classically labeled facultative intracellular pathogens are characterized by the ability to have an intracellular phase in the host, which is required for pathogenicity, while capable of extracellular growth in vitro. the ability of these bacteria to replicate in cell-free conditions is usually assessed by culture in artificial bacteriological media. however, the extracellular growth ability of these pathogens may also be expressed by a phase of extracellular infection in the natural setting of ...201322795971
functional expression of burkholderia cenocepacia xylose isomerase in yeast increases ethanol production from a glucose-xylose blend.this study presents results regarding the successful cloning of the bacterial xylose isomerase gene (xyla) of burkholderia cenocepacia and its functional expression in saccharomyces cerevisiae. the recombinant yeast showed to be competent to efficiently produce ethanol from both glucose and xylose, which are the main sugars in lignocellulosic hydrolysates. the heterologous expression of the gene xyla enabled a laboratorial yeast strain to ferment xylose anaerobically, improving ethanol productio ...201323186665
depletion of the ubiquitin-binding adaptor molecule sqstm1/p62 from macrophages harboring cftr δf508 mutation improves the delivery of burkholderia cenocepacia to the autophagic machinery.cystic fibrosis is the most common inherited lethal disease in caucasians. it is caused by mutations in the cystic fibrosis transmembrane conductance regulator (cftr), of which the cftr δf508 mutation is the most common. δf508 macrophages are intrinsically defective in autophagy because of the sequestration of essential autophagy molecules within unprocessed cftr aggregates. defective autophagy allows burkholderia cenocepacia (b. cepacia) to survive and replicate in δf508 macrophages. infection ...201323148214
an outbreak of burkholderia cenocepacia associated with contaminated chlorhexidine solutions prepared in the hospital.from october to december 2007, an outbreak of burkholderia cenocepacia occurred in a secondary care hospital. the 19 b cenocepacia isolated from the patients, the chlorhexidine solutions of each different ward, and the purified water that diluted these solutions exhibited an identical pulsed-field gel electrophoresis pattern. inadequate preparation of chlorhexidine solutions diluted with contaminated purified water may have resulted in an outbreak of b cenocepacia. adequate preparation of chlorh ...201323608047
podocalyxin is a glycoprotein ligand of the human pluripotent stem cell-specific probe rbc2lcn.in comprehensive glycome analysis with a high-density lectin microarray, we have previously shown that the recombinant n-terminal domain of the lectin bc2l-c from burkholderia cenocepacia (rbc2lcn) binds exclusively to undifferentiated human induced pluripotent stem (ips) cells and embryonic stem (es) cells but not to differentiated somatic cells. here we demonstrate that podocalyxin, a heavily glycosylated type 1 transmembrane protein, is a glycoprotein ligand of rbc2lcn on human ips cells and ...201323526252
novel diagnostic pcr assay for burkholderia cenocepacia epidemic strain st32 and its utility in monitoring infection in cystic fibrosis patients.a highly transmissible burkholderia cenocepacia sequence type (st) 32 strain caused a major outbreak at the prague cystic fibrosis (cf) centre in the late 1990s and early 2000s. because a large number of cf patients were affected by st32, a rapid and easy-to-use diagnostic tool for st32 infection was urgently needed for the detection of new cases as well as for long-term surveillance. the present study sought to identify unique dna sequences within the st32 genome to develop an st32 strain-speci ...201323317764
role of burkholderia cenocepacia afce and afcf genes in determining lipid-metabolism-associated phenotypes.burkholderia cenocepacia is an opportunistic pathogen that primarily infects cystic fibrosis patients. previously we have reported that mutations in shvr, a lysr-type transcriptional regulator, and shvr-regulated genes bcas0208 and bcas0201 (designated afce and afcf, respectively) affect colony morphotype, biofilm and pellicle formation and virulence in b. cenocepacia. in this study we investigated the role of afce and afcf in influencing lipid-metabolism-associated phenotypes. as previously rep ...201323306671
genetic similarity of burkholderia cenocepacia from cystic fibrosis patients.burkholderia cenocepacia may cause serious infections in patients with cystic fibrosis, and this microorganism can be highly transmissible. pulsed-field gel electrophoresis is widely used to study the dynamics of strain spread in cystic fibrosis patients. the aim of this work was to perform pulsed-field gel electrophoresis-based molecular typing of b. cenocepacia isolates to evaluate the epidemiology of this species at our hospital. a total of 28 isolates from 23 cystic fibrosis patients were an ...201323287542
analysis of human bronchial epithelial cell proinflammatory response to burkholderia cenocepacia infection: inability to secrete il-1β.burkholderia cenocepacia, the causative agent of cepacia syndrome, primarily affects cystic fibrosis patients, often leading to death. in the lung, epithelial cells serve as the initial barrier to airway infections, yet their responses to b. cenocepacia have not been fully investigated. here, we examined the molecular responses of human airway epithelial cells to b. cenocepacia infection. infection led to early signaling events such as activation of erk, akt, and nf-κb. further, tnfα, il-6, il-8 ...201323269671
the burkholderia cenocepacia sensor kinase hybrid atsr is a global regulator modulating quorum-sensing signalling.burkholderia cenocepacia is commonly found in the environment and also as an important opportunistic pathogen infecting patients with cystic fibrosis. successful infection by this bacterium requires coordinated expression of virulence factors, which is achieved through different quorum sensing (qs) regulatory systems. biofilm formation and type 6 secretion system (t6ss) expression in b. cenocepacia k56-2 are positively regulated by qs and negatively regulated by the sensor kinase hybrid atsr. th ...201322830644
innate immune sensing of bacterial modifications of rho gtpases by the pyrin inflammasome.cytosolic inflammasome complexes mediated by a pattern recognition receptor (prr) defend against pathogen infection by activating caspase 1. pyrin, a candidate prr, can bind to the inflammasome adaptor asc to form a caspase 1-activating complex. mutations in the pyrin-encoding gene, mefv, cause a human autoinflammatory disease known as familial mediterranean fever. despite important roles in immunity and disease, the physiological function of pyrin remains unknown. here we show that pyrin mediat ...201424919149
immunological function of familial mediterranean fever disease protein pyrin.pyrin, encoded by mefv gene, is conserved in humans and mice. mutations in the mefv gene are associated with the human autoinflammatory disease familial mediterranean fever (fmf). pyrin can interact with the inflammasome adaptor asc and induce inflammatory caspase-1 activation in monocytic cells, but the physiological function of pyrin has been unknown for many years. here we summarize previous studies of pyrin function under the context of fmf and immunity, and discuss a recent study demonstrat ...201425307949
lung transplant for a patient with cystic fibrosis and active burkholderia cenocepacia pneumonia.lung transplant for cystic fibrosis has been considered contraindicated in patients who have burkholderia cenocepacia infection. a 24-year-old white woman who had cystic fibrosis presented with respiratory failure caused by b. cenocepacia pneumonia. she was treated with broad-spectrum antibiotics and a double-lung transplant. the chest cavity and both bronchi were irrigated with 0.5% povidone-iodine solution. for immunosuppression, she received induction therapy with alemtuzumab (15 mg) and meth ...201425299375
parallel evolution of small colony variants in burkholderia cenocepacia biofilms.a common phenotype within bacterial biofilms is the small, "wrinkly" colony, which may associate with worse prognoses from biofilm-associated infections. the mechanisms that produce these variants in burkholderia are undefined. here we report the mutational and ecological causes of wrinkly (w) colonies that evolved during experimental biofilm evolution of burkholderia cenocepacia. mutations clustered in a homologous pathway to the pseudomonas wsp operon but with a distinct terminal signaling mec ...201425263109
a markerless deletion method for genetic manipulation of burkholderia cenocepacia and other multidrug-resistant gram-negative bacteria.genetic manipulation of multidrug-resistant bacteria is often difficult and hinders progress in understanding their physiology and pathogenesis. this book chapter highlights advances in genetic manipulation of burkholderia cenocepacia, which are also applicable to other members of the burkholderia cepacia complex and multidrug-resistant gram-negative bacteria of other genera. the method detailed here is based on the i-scei homing endonuclease system, which can be efficiently used for chromosomal ...201425172289
the bcesm genomic region contains a regulator involved in quorum sensing and persistence in burkholderia cenocepacia j2315.in this study, we investigated the function of bcam0257-8-9 located in the bcesm region of the burkholderia cenocepacia j2315 genome.201425156374
cd4+ t cell epitopes of flic conserved between strains of burkholderia: implications for vaccines against melioidosis and cepacia complex in cystic fibrosis.burkholderia pseudomallei is the causative agent of melioidosis characterized by pneumonia and fatal septicemia and prevalent in southeast asia. related burkholderia species are strong risk factors of mortality in cystic fibrosis (cf). the b. pseudomallei flagellar protein flic is strongly seroreactive and vaccination protects challenged mice. we assessed b. pseudomallei flic peptide binding affinity to multiple hla class ii alleles and then assessed cd4 t cell immunity in hla class ii transgeni ...201425392525
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