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a functional orit in the ptw plasmid of burkholderia cenocepacia can be recognized by the r388 relaxase trwc.burkholderia cenocepacia is both a plant pathogen and the cause of serious opportunistic infections, particularly in cystic fibrosis patients. b. cenocepacia k56-2 harbors a native plasmid named ptw for its involvement in the plant tissue watersoaking phenotype. ptw has also been reported to be important for survival in human cells. interestingly, the presence of ptwc, a homolog of the conjugative relaxase trwc of plasmid r388, suggests a possible function for ptw in conjugative dna transfer. th ...201627200362
draft genome sequence of burkholderia cenocepacia strain ceib s5-2, a methyl parathion- and p-nitrophenol-degrading bacterium, isolated from agricultural soils in morelos, mexico.burkholderia cenocepacia is an opportunistic pathogen that belongs to burkholderia cepacia complex (bcc). burkholderia cenocepacia strain ceib s5-2 was isolated from agricultural soils in morelos, mexico, and previously has shown its abilities for bioremediation. in this study, we report the draft genome sequence of burkholderia cenocepacia strain ceib s5-2.201627125479
tyrosine phosphorylation and dephosphorylation in burkholderia cenocepacia affect biofilm formation, growth under nutritional deprivation, and pathogenicity.burkholderia cenocepacia, a member of the b. cepacia complex (bcc), is an opportunistic pathogen causing serious chronic infections in patients with cystic fibrosis. tyrosine phosphorylation has emerged as an important posttranslational modification modulating the physiology and pathogenicity of bcc bacteria. here, we investigated the predicted bacterial tyrosine kinases bcam1331 and bcef and the low-molecular-weight protein tyrosine phosphatases bcam0208, bced, and bcal2200 of b. cenocepacia k5 ...201626590274
polyphasic characterisation of burkholderia cepaciacomplex species isolated from children with cystic fibrosis.cystic fibrosis (cf) patients with burkholderia cepacia complex (bcc) pulmonary infections have high morbidity and mortality. the aim of this study was to compare different methods for identification of bcc species isolated from paediatric cf patients. oropharyngeal swabs from children with cf were used to obtain isolates of bcc samples to evaluate six different tests for strain identification. conventional (cpt) and automatised (apt) phenotypic tests, polymerase chain reaction (pcr)-reca, restr ...201626814642
crystal structure of bacterial haem importer complex in the inward-facing conformation.pathogenic bacteria remove iron from the haem of host tissues and use it as a catalytic center of many enzymes. haem uptake by pathogenic bacteria is facilitated by the membrane-integrated haem importer, which belongs to the type ii atp-binding cassette (abc) transporter. here we present crystal structures of burkholderia cenocepacia haem importer bhuuv complexed with the periplasmic haem-binding protein bhut and in the absence of bhut. the transmembrane helices of these structures show an inwar ...201627830695
orderly replication and segregation of the four replicons of burkholderia cenocepacia j2315.bacterial genomes typically consist of a single chromosome and, optionally, one or more plasmids. but whole-genome sequencing reveals about ten per-cent of them to be multipartite, with additional replicons which by size and indispensability are considered secondary chromosomes. this raises the questions of how their replication and partition is managed without compromising genome stability and of how such genomes arose. vibrio cholerae, with a 1 mb replicon in addition to its 3 mb chromosome, i ...201627428258
structural differences in gut bacteria communities in developmental stages of natural populations of lutzomyia evansi from colombia's caribbean coast.lutzomyia evansi, a phlebotomine insect endemic to colombia's caribbean coast, is considered to be the main vector of visceral and cutaneous leishmaniasis in the region. although insects of this species can harbor pathogenic and non-pathogenic microorganisms in their intestinal microbiota, there is little information available about the diversity of gut bacteria present in lutzomyia evansi. in this study, conventional microbiological methods and molecular tools were used to assess the compositio ...201627618991
destruction of opportunistic pathogens via polymer nanoparticle-mediated release of plant-based antimicrobial payloads.the synthesis of antimicrobial thymol/carvacrol-loaded polythioether nanoparticles (nps) via a one-pot, solvent-free miniemulsion thiol-ene photopolymerization process is reported. the active antimicrobial agents, thymol and carvacrol, are employed as "solvents" for the thiol-ene monomer phase in the miniemulsion to enable facile high capacity loading (≈50% w/w), excellent encapsulation efficiencies (>95%), and elimination of all postpolymerization purification processes. the nps serve as high c ...201626946055
the dsf type quorum sensing signalling system rpff/r regulates diverse phenotypes in the opportunistic pathogen cronobacter.several bacterial pathogens produce diffusible signal factor (dsf)-type quorum sensing (qs) signals to control biofilm formation and virulence. previous work showed that in burkholderia cenocepacia the rpffbc/rpfr system is involved in sensing and responding to dsf signals and that this signal/sensor gene pair is highly conserved in several bacterial species including cronobacter spp. here we show that c. turicensis lmg 23827(t) possesses a functional rpff/r system that is involved in the regula ...201626725701
lipopolysaccharide modification in gram-negative bacteria during chronic infection.the gram-negative bacterial lipopolysaccharide (lps) is a major component of the outer membrane that plays a key role in host-pathogen interactions with the innate immune system. during infection, bacteria are exposed to a host environment that is typically dominated by inflammatory cells and soluble factors, including antibiotics, which provide cues about regulation of gene expression. bacterial adaptive changes including modulation of lps synthesis and structure are a conserved theme in infect ...201627075488
laboratory evolution of microbial interactions in bacterial biofilms.microbial adaptation is conspicuous in essentially every environment, but the mechanisms of adaptive evolution are poorly understood. studying evolution in the laboratory under controlled conditions can be a tractable approach, particularly when new, discernible phenotypes evolve rapidly. this is especially the case in the spatially structured environments of biofilms, which promote the occurrence and stability of new, heritable phenotypes. further, diversity in biofilms can give rise to nascent ...201627044625
fish oils against burkholderia and pseudomonas aeruginosa: in vitro efficacy and their therapeutic and prophylactic effects on infected galleria mellonella larvae.this study investigates the antimicrobial effects of fish oil-based formulas rich in omega-3 fatty acids (free fatty acids, ethyl esters or triacylglycerols), against cystic fibrosis (cf) pathogens (burkholderia cenocepacia k56-2 and pseudomonas aeruginosa pao1), often resistant to multiple antibiotics.201627012860
elevated mirc1/mir17-92 cluster expression negatively regulates autophagy and cftr (cystic fibrosis transmembrane conductance regulator) function in cf macrophages.cystic fibrosis (cf) is a fatal, genetic disorder that critically affects the lungs and is directly caused by mutations in the cf transmembrane conductance regulator (cftr) gene, resulting in defective cftr function. macroautophagy/autophagy is a highly regulated biological process that provides energy during periods of stress and starvation. autophagy clears pathogens and dysfunctional protein aggregates within macrophages. however, this process is impaired in cf patients and cf mice, as their ...201627541364
the crystal structure of burkholderia cenocepacia dfsa provides insights into substrate recognition and quorum sensing fatty acid biosynthesis.burkholderia cenocepacia is a major concern among respiratory tract infections in cystic fibrosis patients. this pathogen is particularly difficult to treat because of its high level of resistance to the clinically relevant antimicrobial agents. in b. cenocepacia, the quorum sensing cell-cell communication system is involved in different processes that are important for bacterial virulence, such as biofilm formation and protease and siderophore production. targeting the enzymes involved in this ...201627198181
arnt proteins that catalyze the glycosylation of lipopolysaccharide share common features with bacterial n-oligosaccharyltransferases.arnt is a glycosyltransferase that catalyzes the addition of 4-amino-4-deoxy-l-arabinose (l-ara4n) to the lipid a moiety of the lipopolysaccharide. this is a critical modification enabling bacteria to resist killing by antimicrobial peptides. arnt is an integral inner membrane protein consisting of 13 predicted transmembrane helices and a large periplasmic c-terminal domain. we report here the identification of a functional motif with a canonical consensus sequence dexryax(5)mx(3)gxwx(9)yfekpx(4 ...201626515403
mouse intestinal niche cells express a distinct α1,2-fucosylated glycan recognized by a lectin from burkholderia cenocepacia.in this study, we examined the distribution of fucosylated glycans in mouse intestines using a lectin, bc2lcn (n-terminal domain of the lectin bc2l-c from burkholderia cenocepacia), as a probe. bc2lcn is specific for glycans with a terminal fucα1,2galβ1,3-motif and it is a useful marker for discriminating the undifferentiated status of human induced/embryonic stem cells. apparent bc2lcn reactivity was detected in the secretory granules of goblet cells in the ileum but not those in the colon. we ...201627979999
biofilms produced by burkholderia cenocepacia: influence of media and solid supports on composition of matrix exopolysaccharides.bacteria usually grow forming biofilms, which are communities of cells embedded in a self-produced dynamic polymeric matrix, characterized by a complex three-dimensional structure. the matrix holds cells together and above a surface, and eventually releases them, resulting in colonization of other surfaces. although exopolysaccharides (epols) are important components of the matrix, determination of their structure is usually performed on samples produced in non-biofilm conditions, or indirectly ...201626586192
combination antimicrobial susceptibility testing of burkholderia cepacia complex: significance of species.the burkholderia cepacia complex (bcc) is notorious for the life-threatening pulmonary infections it causes in patients with cystic fibrosis. the multidrug-resistant nature of bcc and differing infective bcc species make the design of appropriate treatment regimens challenging. previous synergy studies have failed to take account of the species of bcc isolates. etest methodology was used to facilitate minimum inhibitory concentration (mic) and antimicrobial combination testing on 258 isolates of ...201627665523
a burkholderia type vi effector deamidates rho gtpases to activate the pyrin inflammasome and trigger inflammation.burkholderia cenocepacia is an opportunistic pathogen of the cystic fibrosis lung that elicits a strong inflammatory response. b. cenocepacia employs a type vi secretion system (t6ss) to survive in macrophages by disarming rho-type gtpases, causing actin cytoskeletal defects. here, we identified teca, a non-vgrg t6ss effector responsible for actin disruption. teca and other bacterial homologs bear a cysteine protease-like catalytic triad, which inactivates rho gtpases by deamidating a conserved ...201627133449
in vitro volatile organic compound profiling using gc×gc-tofms to differentiate bacteria associated with lung infections: a proof-of-concept study.chronic pulmonary infections are the principal cause of morbidity and mortality in individuals with cystic fibrosis (cf). due to the polymicrobial nature of these infections, the identification of the particular bacterial species responsible is an essential step in diagnosis and treatment. current diagnostic procedures are time-consuming, and can also be expensive, invasive and unpleasant in the absence of spontaneously expectorated sputum. the development of a rapid, non-invasive methodology ca ...201627120170
an erp57-mediated disulphide exchange promotes the interaction between burkholderia cenocepacia and epithelial respiratory cells.previous studies have demonstrated that extracellular glutathione reduces the ability of the cystic fibrosis pathogen burkholderia cenocepacia to infect primary or immortalized epithelial respiratory cells. we report here that the adhesion and invasion ability of b. cenocepacia is limited also by thiol-oxidizing and disulphide-reducing agents and by protein disulfide isomerase (pdi) inhibitors. pdi inhibitors also reduce the proinflammatory response elicited by cells in response to burkholderia. ...201626879174
activator of g-protein signaling 3-induced lysosomal biogenesis limits macrophage intracellular bacterial infection.many intracellular pathogens cause disease by subverting macrophage innate immune defense mechanisms. intracellular pathogens actively avoid delivery to or directly target lysosomes, the major intracellular degradative organelle. in this article, we demonstrate that activator of g-protein signaling 3 (ags3), an lps-inducible protein in macrophages, affects both lysosomal biogenesis and activity. ags3 binds the gi family of g proteins via its g-protein regulatory (goloco) motif, stabilizing the g ...201626667172
burkholderia cenocepacia virulence microevolution in the cf lung: variations on a theme. 201627786605
the fitness effects of spontaneous mutations nearly unseen by selection in a bacterium with multiple chromosomes.mutation accumulation (ma) experiments employ the strategy of minimizing the population size of evolving lineages to greatly reduce effects of selection on newly arising mutations. thus, most mutations fix within ma lines independently of their fitness effects. this approach, more recently combined with genome sequencing, has detailed the rates, spectra, and biases of different mutational processes. however, a quantitative understanding of the fitness effects of mutations virtually unseen by sel ...201627672096
variation of burkholderia cenocepacia virulence potential during cystic fibrosis chronic lung infection.during long-term lung infection in cystic fibrosis (cf) patients, burkholderia cenocepacia faces multiple selective pressures in this highly stressful and fluctuating environment. as a consequence, the initial infecting strain undergoes genetic changes that result in the diversification of genotypes and phenotypes. whether this clonal expansion influences the pathogenic potential is unclear. the virulence potential of 39 sequential b. cenocepacia (reca lineage iiia) isolates, corresponding to 3 ...201627652671
eradication and phenotypic tolerance of burkholderia cenocepacia biofilms exposed to atmospheric pressure non-thermal plasma.chronic lung infection with bacteria from the burkholderia cepacia complex (bcc), and in particular b. cenocepacia, is associated with significant morbidity and mortality in patients with cystic fibrosis (cf). b. cenocepacia can spread from person to person and exhibits intrinsic broad-spectrum antibiotic resistance. recently, atmospheric pressure non-thermal plasmas (apntps) have gained increasing attention as a novel approach to the prevention and treatment of a variety of hospital-acquired in ...201627179816
the temperate burkholderia phage ap3 of the peduovirinae shows efficient antimicrobial activity against b. cenocepacia of the iiia lineage.burkholderia phage ap3 (vb_bcem_ap3) is a temperate virus of the myoviridae and the peduovirinae subfamily (p2likevirus genus). this phage specifically infects multidrug-resistant clinical burkholderia cenocepacia lineage iiia strains commonly isolated from cystic fibrosis patients. ap3 exhibits high pairwise nucleotide identity (61.7 %) to burkholderia phage ks5, specific to the same b. cenocepacia host, and has 46.7-49.5 % identity to phages infecting other species of burkholderia. the lysis c ...201727770178
the effect of mutation in the clpx gene on the synthesis of n-acyl-homoserine lactones and other properties of burkholderia cenocepacia 370.in order to study the regulation of n-acyl-homoserine lactones synthesis (ahls, the signal molecules of quorum sensing regulation) in burkholderia cenocepacia strain 370 we obtained mutants with increased ahl production. one of the mutants, named bc-b6, was obtained by tnmod-rkm(r) plasposon mutagenesis. the plasposon insertion was located within the clpx gene encoding the atpase subunit clpx of the clpxp protease. the mutation reduced bacterial virulence in mice intranasal infection. the result ...201727242147
competitive growth enhances conditional growth mutant sensitivity to antibiotics and exposes a two-component system as an emerging antibacterial target in burkholderia cenocepacia.chemogenetic approaches to profile an antibiotic mode of action are based on detecting differential sensitivities of engineered bacterial strains in which the antibacterial target (usually encoded by an essential gene) or an associated process is regulated. we previously developed an essential-gene knockdown mutant library in the multidrug-resistant burkholderia cenocepacia by transposon delivery of a rhamnose-inducible promoter. in this work, we used illumina sequencing of multiplex-pcr-amplifi ...201727799222
the burkholderia cenocepacia peptidoglycan-associated lipoprotein is involved in epithelial cell attachment and elicitation of inflammation.the burkholderia cepacia complex (bcc) is a group of gram-negative opportunistic pathogens causing infections in people with cystic fibrosis (cf). bcc is highly antibiotic resistant, making conventional antibiotic treatment problematic. the identification of novel targets for anti-virulence therapies should improve therapeutic options for infected cf patients. we previously identified that the peptidoglycan-associated lipoprotein (pal) was immunogenic in bcc infected cf patients; however, its ro ...201727886433
burkholderia cenocepacia k56-2 trimeric autotransporter adhesin bcaa binds tnfr1 and contributes to induce airway inflammation.chronic lung disease caused by persistent bacterial infections is a major cause of morbidity and mortality in patients with cystic fibrosis (cf). cf pathogens acquire antibiotic resistance, overcome host defenses, and impose uncontrolled inflammation that ultimately may cause permanent damage of lungs' airways. among the multiple cf-associated pathogens, burkholderia cenocepacia and other burkholderia cepacia complex bacteria have become prominent contributors of disease progression. here, we de ...201727684048
human cystic fibrosis macrophages have defective calcium-dependent protein kinase c activation of the nadph oxidase, an effect augmented by burkholderia cenocepacia.macrophage intracellular pathogen killing is defective in cystic fibrosis (cf), despite abundant production of reactive oxygen species (ros) in lung tissue. burkholderia species can cause serious infection in cf and themselves affect key oxidase components in murine non-cf cells. however, it is unknown whether human cf macrophages have an independent defect in the oxidative burst and whether burkholderia contributes to this defect in terms of assembly of the nadph oxidase complex and subsequent ...201728093527
the lpxl acyltransferase is required for normal growth and penta-acylation of lipid a in burkholderia cenocepacia.lipid a anchors the lipopolysaccharide (lps) to the outer membrane and is usually composed of a hexa-acylated diglucosamine backbone. burkholderia cenocepacia, an opportunistic pathogen, produces a mixture of tetra- and penta-acylated lipid a. "late" acyltransferases add secondary acyl chains to lipid a after the incorporation of four primary acyl chains to the diglucosamine backbone. here, we report that b. cenocepacia has only one late acyltransferase, lpxl (bcal0508), which adds a myristoyl c ...201728085228
cheating fosters species co-existence in well-mixed bacterial communities.explaining the enormous biodiversity observed in bacterial communities is challenging because ecological theory predicts that competition between species occupying the same niche should lead to the exclusion of less competitive community members. competitive exclusion should be particularly strong when species compete for a single limiting resource or live in unstructured habitats that offer no refuge for weaker competitors. here, we describe the 'cheating effect', a form of intra-specific compe ...201728060362
using dendritic cells to evaluate how burkholderia cenocepacia clonal isolates from a chronically infected cystic fibrosis patient subvert immune functions.infection with burkholderia cepacia complex (bcc) bacteria is a threat to cystic fibrosis (cf) patients, commonly leading to a fatal pneumonia, the cepacia syndrome. it causes a massive production of pro-inflammatory cytokines and leucocyte recruitment to airway epithelium without resolving infection and contributing to tissue lesion. to dissect how bcc bacteria subvert the immune response, we developed a co-culture model with human dendritic cells (dcs) and b. cenocepacia clonal variants isolat ...201727987042
tri- and tetravalent mannoclusters cross-link and aggregate bc2l-a lectin from burkholderia cenocepacia.the opportunistic gram-negative bacterium burkholderia cenocepacia causes lethal infections in cystic fibrosis patients. multivalent mannoside derivatives were prepared as potential inhibitors of lectin bc2l-a, one of the virulence factors deployed by b. cenocepacia in the infection process. an (α1→2)-thio-linked mannobioside mimic bearing an azide functionalized aglycon was conjugated to different multivalent scaffolds such as propargylated calix[4]arenes, methyl gallate and pentaerythritol by ...201727871013
bacterial proteases and haemostasis dysregulation in the cf lung.pathogenic bacteria which chronically colonise the cystic fibrosis (cf) lung produce a number of virulence determinants, including distinct proteolytic activities. the potential role bacterial proteases play on haemostatic dysregulation within the cf lung is, however, poorly defined, despite haemoptysis being a common complication in cf.201727839953
an efficient system for the generation of marked genetic mutants in members of the genus burkholderia.to elucidate the function of a gene in bacteria it is vital that targeted gene inactivation (allelic replacement) can be achieved. allelic replacement is often carried out by disruption of the gene of interest by insertion of an antibiotic-resistance marker followed by subsequent transfer of the mutant allele to the genome of the host organism in place of the wild-type gene. however, due to their intrinsic resistance to many antibiotics only selected antibiotic-resistance markers can be used in ...201727825973
identification and analysis of genomic islands in burkholderia cenocepacia au 1054 with emphasis on pathogenicity islands.genomic islands (gis) are genomic regions that reveal evidence of horizontal dna transfer. they can code for many functions and may augment a bacterium's adaptation to its host or environment. gis have been identified in strain j2315 of burkholderia cenocepacia, whereas in strain au 1054 there has been no published works on such regions according to our text mining and keyword search in medline.201728347342
phenotypic diversity and genotypic flexibility of burkholderia cenocepacia during long-term chronic infection of cystic fibrosis lungs.chronic bacterial infections of the lung are the leading cause of morbidity and mortality in cystic fibrosis patients. tracking bacterial evolution during chronic infections can provide insights into how host selection pressures-including immune responses and therapeutic interventions-shape bacterial genomes. we carried out genomic and phenotypic analyses of 215 serially collected burkholderia cenocepacia isolates from 16 cystic fibrosis patients, spanning a period of 2-20 yr and a broad range o ...201728325850
peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity.cationic antimicrobial peptides (camps) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. herein, we report a strategy that can lead to the discovery of novel small camps with greatly enhanced antimicrobial activity and retained antibiofilm potential. we geared our efforts towards i) the n-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, krfrirvr ...201728296935
sequential burkholderia cenocepacia isolates from siblings with cystic fibrosis show increased lung cell attachment. 201728294652
evaluation of combination therapy for burkholderia cenocepacia lung infection in different in vitro and in vivo models.burkholderia cenocepacia is an opportunistic pathogen responsible for life-threatening infections in cystic fibrosis patients. b. cenocepacia is extremely resistant towards antibiotics and therapy is complicated by its ability to form biofilms. we investigated the efficacy of an alternative antimicrobial strategy for b. cenocepacia lung infections using in vitro and in vivo models. a screening of the nih clinical collection 1&2 was performed against b. cenocepacia biofilms formed in 96-well micr ...201728248999
biocontrol of burkholderia cepacia complex bacteria and bacterial phytopathogens by bdellovibrio bacteriovorus.bdellovibrio and like organisms are predatory bacteria that have the unusual property of using the cytoplasmic constituents of other gram-negative bacteria as nutrients. these predators may thus provide an alternative approach to the biocontrol of human and plant pathogens. predators were isolated on burkholderia cenocepacia k56-2 and j2315 as prey cells, in enrichment cultures with soil and sewage. three isolates (dm7c, dm8a, and dm11a) were identified as bdellovibrio bacteriovorus on the basis ...201728177793
mouse intestinal niche cells express a distinct α1,2-fucosylated glycan recognized by a lectin from burkholderia cenocepacia. 201728177462
synthetic cystic fibrosis sputum medium diminishes <i>burkholderia cenocepacia</i> antifungal activity against <i>aspergillus fumigatus</i> independently of phenylacetic acid production.phenylacetic acid (paa), an intermediate of phenylalanine degradation, is emerging as a signal molecule in microbial interactions with the host. in this work, we explore the presence of phenylalanine and paa catabolism in three microbial pathogens of the cystic fibrosis (cf) lung microbiome: <i>pseudomonas aeruginosa</i>, <i>burkholderia cenocepacia</i> and <i>aspergillus fumigatus</i>. while <i>in silico</i> analysis of <i>b. cenocepacia</i> j2315 and <i>a. fumigatus</i> af293 genome sequences ...201728178425
antibiotic capture by bacterial lipocalins uncovers an extracellular mechanism of intrinsic antibiotic resistance.the potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. here we show that a soluble bacterial lipocalin produced by burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo these phenotypes were recapitulated by heterologous expression in b. cenocepacia of lipocalin genes from pseudomonas aeruginosa, mycobacterium tuberculosis, and methici ...201728292982
a broad host range tailocin from burkholderia cenocepacia.the burkholderia cepacia complex (bcc) consists of 20 closely related gram-negative bacterial species that are significant pathogens for persons with cystic fibrosis (cf). some bcc strains are highly transmissible and resistant to multiple antibiotics, making infection difficult to treat. a tailocin (phage-tail-like bacteriocin), designated bcetmilo, with broad host range against members of the bcc was identified in burkholderia cenocepacia strain bc0425. sixty-eight percent of bcc representing ...201728258146
lactoferrin decreases inflammatory response by cystic fibrosis bronchial cells invaded with burkholderia cenocepacia iron-modulated biofilm.in cystic fibrosis (cf) high iron concentration in airway secretion plays a pivotal role in bacterial multiplication and biofilm formation as well as in inflammatory response. burkholderia cenocepacia, an opportunistic facultative pathogen responsible for chronic lung infections and cepacia syndrome, recurrently infects cf patients. lactoferrin (lf), an iron binding multifunctional glycoprotein synthesized by exocrine glands and neutrophils, has been found at higher concentration in the airway s ...201722230411
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