The involvement of the low-oxygen-activated locus of Burkholderia cenocepacia in adaptation during cystic fibrosis infection.

Chronic infection with opportunistic pathogens including Burkholderia cepacia complex (Bcc) is a hallmark of cystic fibrosis (CF). We investigated the adaptive mechanisms facilitating chronic lung infection in sequential Bcc isolates from two siblings with CF (P1 and P2), one of whom also experienced intermittent blood-stream infections (P2). We previously showed increased lung cell attachment with colonisation time in both P1 and P2.

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.

Linocin and OmpW Are Involved in Attachment of the Cystic Fibrosis-Associated Pathogen Burkholderia cepacia Complex to Lung Epithelial Cells and Protect Mice against Infection.

Members of the Burkholderia cepacia complex (Bcc) cause chronic opportunistic lung infections in people with cystic fibrosis (CF), resulting in a gradual lung function decline and, ultimately, patient death. The Bcc is a complex of 20 species and is rarely eradicated once a patient is colonized; therefore, vaccination may represent a better therapeutic option. We developed a new proteomics approach to identify bacterial proteins that are involved in the attachment of Bcc bacteria to lung epithelial cells.

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies.

Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and species-specific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens.

Investigation of the multifaceted iron acquisition strategies of Burkholderia cenocepacia.

Burkholderia cenocepacia is a bacterial pathogen which causes severe respiratory infections in cystic fibrosis (CF). These studies were aimed at gaining an insight into the iron acquisition strategies of B. cenocepacia.

The tyrosine kinase BceF and the phosphotyrosine phosphatase BceD of Burkholderia contaminans are required for efficient invasion and epithelial disruption of a cystic fibrosis lung epithelial cell line.

Bacterial tyrosine kinases and their cognate protein tyrosine phosphatases are best known for regulating the biosynthesis of polysaccharides. Moreover, their roles in the stress response, DNA metabolism, cell division, and virulence have also been documented. The aim of this study was to investigate the pathogenicity and potential mechanisms of virulence dependent on the tyrosine kinase BceF and phosphotyrosine phosphatase BceD of the cystic fibrosis opportunistic pathogen Burkholderia contaminans IST408.

Chemistry of lipid A: at the heart of innate immunity.

In many Gram-negative bacteria, lipopolysaccharide (LPS) and its lipid A moiety are pivotal for bacterial survival. Depending on its structure, lipid A carries the toxic properties of the LPS and acts as a potent elicitor of the host innate immune system via the Toll-like receptor 4/myeloid differentiation factor 2 (TLR4/MD-2) receptor complex. It often causes a wide variety of biological effects ranging from a remarkable enhancement of the resistance to the infection to an uncontrolled and massive immune response resulting in sepsis and septic shock.

The evolving dynamics of the microbial community in the cystic fibrosis lung.

The cystic fibrosis (CF) lung is a niche colonized by a diverse group of organisms, with a more limited number of species including Pseudomonas aeruginosa dominating in adult patients. Whether all members of this microbial community play a direct or indirect role in pulmonary decline has yet to be fully elucidated, but investigations of their interactions with both co-colonizing species and with host cells are beginning to shed light on their virulence potential. It is also emerging that some microbial species within this community adapt as chronic infection is established to survive the hostile environment of the lung, to minimize host clearance and to resist therapeutic intervention.

Inhibition of co-colonizing cystic fibrosis-associated pathogens by Pseudomonas aeruginosa and Burkholderia multivorans.

Cystic fibrosis (CF) is a recessive genetic disease characterized by chronic respiratory infections and inflammation causing permanent lung damage. Recurrent infections are caused by Gram-negative antibiotic-resistant bacterial pathogens such as Pseudomonas aeruginosa, Burkholderia cepacia complex (Bcc) and the emerging pathogen genus Pandoraea. In this study, the interactions between co-colonizing CF pathogens were investigated.

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.

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.

Inhibition of Burkholderia multivorans adhesion to lung epithelial cells by bivalent lactosides.

Burkholderia cepacia complex (Bcc) is an opportunistic pathogen in cystic fibrosis patients which is inherently resistant to antimicrobial agents. The mechanisms of attachment and pathogenesis of Bcc, a group of 17 species, are poorly understood. The most commonly identified Bcc species in newly colonised patients, Burkholderia multivorans, continues to be acquired from the environment.

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.

Bacterial host interactions in cystic fibrosis.

Chronic infection is a hallmark of cystic fibrosis (CF) and the main contributor to morbidity. Microbial infection in CF is complex, due to the number of different species that colonise the CF lung. Their colonisation is facilitated by a host response that is impaired or compromised by highly viscous mucous, zones of hypoxia and the lack of the cystic fibrosis transmembrane regulator (CFTR).

Activation of MMP-9 by human lung epithelial cells in response to the cystic fibrosis-associated pathogen Burkholderia cenocepacia reduced wound healing in vitro.

Burkholderia cepacia complex is a group of bacterial pathogens that cause opportunistic infections in cystic fibrosis (CF). The most virulent of these is Burkholderia cenocepacia. Matrix metalloproteinases (MMPs) are upregulated in CF patients.

Virulence of an emerging respiratory pathogen, genus Pandoraea, in vivo and its interactions with lung epithelial cells.

Pandoraea species have emerged as opportunistic pathogens among cystic fibrosis (CF) and non-CF patients. Pandoraea pulmonicola is the predominant Pandoraea species among Irish CF patients. The objective of this study was to investigate the pathogenicity and potential mechanisms of virulence of Irish P.

IL-8 released from human lung epithelial cells induced by cystic fibrosis pathogens Burkholderia cepacia complex affects the growth and intracellular survival of bacteria.

Burkholderia cepacia complex (Bcc) is a group of Gram-negative pulmonary pathogens associated with life-threatening infections in patients with cystic fibrosis (CF). The airway epithelium plays a crucial role in the initiation and modulation of inflammatory responses to these pathogens. Interleukin (IL)-8 released from epithelial cells is a potent chemoattractant for neutrophils.

Invasion of Burkholderia cepacia complex isolates into lung epithelial cells involves glycolipid receptors.

Burkholderia cepacia complex (Bcc) is a group of opportunistic cystic fibrosis (CF) pathogens that invade lung epithelial cells. The mechanisms of invasion are poorly understood, in particular, the receptors utilised by this bacterium in the invasion process have not been identified. The aim of this study was to investigate the epithelial receptors involved in the invasion of Bcc isolates.

Macrophage responses to CF pathogens: JNK MAP kinase signaling by Burkholderia cepacia complex lipopolysaccharide.

Chronic bacterial colonization of the airways with opportunistic pathogens is the primary cause of morbidity and mortality in cystic fibrosis (CF) patients. Burkholderia cepacia complex (Bcc) organisms pose a particular challenge in CF lung disease, due in part to their ability to trigger a fulminant pneumonia. This study compares the U937 macrophage response to two Bcc species, B.

Burkholderia cepacia complex: epithelial cell-pathogen confrontations and potential for therapeutic intervention.

Burkholderia cepacia complex (Bcc) is an important and virulent pathogen in cystic fibrosis patients. The interactions between this pathogen and the host lung epithelium are being widely investigated but remain to be elucidated. The complex is very versatile and its interactions with the lung epithelial cells are many and varied.

Evaluation of in vitro virulence characteristics of the genus Pandoraea in lung epithelial cells.

Pandoraea species are emerging opportunistic pathogens capable of causing chronic lung infections in cystic fibrosis patients. This study examined the interactions of 17 Pandoraea isolates from the five identified species (Pandoraea apista, Pandoraea norimbergensis, Pandoraea pulmonicula, Pandoraea sputorum and Pandoraea pnomenusa) plus two Pandoraea genomospecies isolates with lung epithelial cells and their ability to form biofilms in vitro. Only three isolates showed an ability to invade A549 lung epithelial cells, and only one isolate was able to form biofilms.

The effect of recombinant human lactoferrin on growth and the antibiotic susceptibility of the cystic fibrosis pathogen Burkholderia cepacia complex when cultured planktonically or as biofilms.

Objectives: The cystic fibrosis (CF) pathogen Burkholderia cepacia complex (Bcc) is innately resistant to antibiotics and the development of effective therapeutic strategies to treat these infections is a major challenge. The objectives of this study were to investigate the effects of recombinant human lactoferrin (rHL) on planktonic and biofilm cultures of Bcc organisms and to establish whether lactoferrin alters the susceptibility of these cultures to a range of antibiotic therapies.

Methods: Planktonic and biofilm cultures of strains representative of three species of Bcc, Burkholderia multivorans, Burkholderia cenocepacia and Burkholderia dolosa, were exposed to 0-900 mg/L lactoferrin over 0-48 h.

Differences in invasion and translocation of Burkholderia cepacia complex species in polarised lung epithelial cells in vitro.

In order to investigate the mechanisms by which Burkholderia cepacia complex (Bcc) strains cross the epithelial barrier of the lung and cause septicaemia in a subgroup of Cystic Fibrosis (CF) patients, the invasiveness of four Bcc species have been examined in three lung epithelial cells: A549, 16HBE14o- and Calu-3. The latter two cell lines form polarised monolayers when grown on filters. Invasion of both cell lines by B.

Invasion and biofilm formation of Burkholderia dolosa is comparable with Burkholderia cenocepacia and Burkholderia multivorans.

Background: Colonisation with Burkholderia cepacia complex pathogens has been associated with accelerated decline in cystic fibrosis (CF) patients. The two most common species among the CF community are Burkholderia cenocepacia and Burkholderia multivorans. However, Burkholderia dolosa has recently been causing concern due to its transmissibility and virulence in CF patients.