Open Access. Powered by Scholars. Published by Universities.®
- Institution
- Publication
- Publication Type
- File Type
Articles 1 - 14 of 14
Full-Text Articles in Life Sciences
Protein With Negative Surface Charge Distribution, Bnr1, Shows Characteristics Of Adna‐Mimic Protein Andmay Be Involved In The Adaptation Of Burkholderia Cenocepacia, Ruth Dennehy, Niamh Duggan, Simon Dignam, Sarah Mccormack, Eugene Dillon, Jessica Molony, Maria Romano, Yueran Hou, Laura Ardill, Matthew Whelan, Zuzanna Drulis‐Kawa, Tadhg Ó'Cróinín, Miguel Valvano, Rita Berisio, Siobhán Mcclean
Protein With Negative Surface Charge Distribution, Bnr1, Shows Characteristics Of Adna‐Mimic Protein Andmay Be Involved In The Adaptation Of Burkholderia Cenocepacia, Ruth Dennehy, Niamh Duggan, Simon Dignam, Sarah Mccormack, Eugene Dillon, Jessica Molony, Maria Romano, Yueran Hou, Laura Ardill, Matthew Whelan, Zuzanna Drulis‐Kawa, Tadhg Ó'Cróinín, Miguel Valvano, Rita Berisio, Siobhán Mcclean
Articles
Adaptation of opportunistic pathogens to their host environment requires reprogramming of a vast array of genes to facilitate survival in the host. Burkholderia cenocepacia, a Gram-negative bacterium with a large genome of ∼8 Mb that colonizes environmental niches, is exquisitely adaptable to the hypoxic environment of the cystic fibrosis lung and survives in macrophages. We previously identified an immunoreactive acidic protein encoded on replicon 3, BCAS0292. Deletion of the BCAS0292 gene significantly altered the abundance of 979 proteins by 1.5-fold or more; 19 proteins became undetectable while 545 proteins showed ≥1.5-fold reduced abundance, suggesting the BCAS0292 protein is a …
Metabolic Modeling Of Cystic Fibrosis Airway Microbiota From Patient Samples, Arsh Vyas
Metabolic Modeling Of Cystic Fibrosis Airway Microbiota From Patient Samples, Arsh Vyas
Masters Theses
Cystic Fibrosis (CF) is a genetic disorder, found with higher prevalence in the Caucasian population, affecting > 30,000 individuals in the United States and > 70,000 worldwide. Due to the astoundingly high rate of mortality among CF patients being attributed to respiratory failure brought on by chronic bacterial infections and subsequent airway inflammation, there has been a lot of focus on systematically analyzing CF lung airway communities. While it is observed traditionally that Pseudomonas aeruginosa is the most threatening and persistent CF colonizer due to high antibiotic resistance, recent studies have elicited the roles of other pathogens and it has been widely …
Investigation Of The Growth And Survival Of Staphylococcus Aureus In Cftr-Deficient Macrophages, Bita Azad
Investigation Of The Growth And Survival Of Staphylococcus Aureus In Cftr-Deficient Macrophages, Bita Azad
Electronic Thesis and Dissertation Repository
Staphylococcus aureus and its small colony variants (SCVs) are commonly isolated from the lungs of cystic fibrosis (CF) patients. Although studies have suggested that cystic fibrosis transmembrane regulator (CFTR)-deficient macrophages are diminished in their ability to kill intracellular pathogens, whether this is true for CFTR-deficient macrophages infected with S. aureus or its SCVs is unknown. I employed gentamicin protection and eFluorÔ-670-based proliferation assays to assess the intracellular replication of S. aureus in CFTR inhibitor treated THP-1 and primary human macrophages, and in primary macrophages derived from CF patient blood. My work shows that the susceptibility of CFTR-deficient macrophages to the …
The Effect Of Stenotrophomonas Maltophilia On Gram-Negative Cystic Fibrosis Pathogens., Joshua D Stewart
The Effect Of Stenotrophomonas Maltophilia On Gram-Negative Cystic Fibrosis Pathogens., Joshua D Stewart
College of Arts & Sciences Senior Honors Theses
Cystic Fibrosis (CF) is the most common lethal genetic disorder in the Caucasian population with an incidence of 1 per 3,000 live births and a median predicted survival of only 47 years. Respiratory failure due to repeated pathological insults to lung tissue by infection is the ultimate cause of mortality in the majority of patients. The lung microenvironment created by CF highly favors colonization by opportunistic pathogens such as Pseudomonas aeruginosa, Stenotrophomonas maltophilia, Burkholderia cenocepacia, and Achromobacter xylosoxidans. Biofilm formation by multiple bacterial species contributes to the chronic, persistent, and difficult to treat nature of CF infections. This study seeks …
Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin
Iron-Containing Nanoparticles For The Treatment Of Chrionic Biofilm Infections In Cystic Fibrosis, Leisha M. A. Martin
Nanoscience and Microsystems ETDs
Cystic fibrosis (CF) is the most common genetic disease resulting in the morbidity and mortality of Caucasian children and adults worldwide. Due to a genetic mutation resulting in malfunction of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, CF patients produce highly viscous mucus in their respiratory tract. This leads to impairment of the mucociliary clearance of inhaled microbes. In addition to reduced microbial clearance, anoxic environmental conditions in the lungs promote biofilm-mode growth of the pathogenic bacterial species Pseudomonas aeruginosa. Chronic infections of P. aeruginosa begin in early childhood and typically persist until respiratory failure and death result. The …
Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow
Expression Profiling Of Non-Coding Rna By Environmental Interactions In Innate Immunity, Jacob R. Longfellow
Electronic Theses and Dissertations
Cystic fibrosis (CF) is a genetic disorder that affects 30,000 people in the United States and currently has no cure. Although CF affects all of the body’s systems, it is largely characterized as a lung disease. CF is caused by a mutation in both copies of the gene for cystic fibrosis transmembrane conductance regulator (CFTR). A mutation in the CFTR gene leads to improper movement of chloride ions and water into the airways, which dysregulates the airway surface liquid volume and composition. Individuals with CF are prone to lung infections due to inefficient bacterial clearance and by the age of …
Burkholderia Cenocepacia J2315-Mediated Destruction Of Staphylococcus Aureus Nrs77 Biofilms., Rachel Thompson
Burkholderia Cenocepacia J2315-Mediated Destruction Of Staphylococcus Aureus Nrs77 Biofilms., Rachel Thompson
College of Arts & Sciences Senior Honors Theses
Cystic fibrosis (CF) is an inherited disorder that affects over 30,000 people in the US and more than 70,000 people worldwide. Recurring bacterial infections in CF patients result in tissue damage that dramatically lowers respiratory function and are ultimately fatal. The formation of bacterial biofilms in the mucus and on lung epithelial tissue allows pathogens to be protected from antibiotics and the host immune system, making treatment of infection difficult. The interactions between CF pathogens in co-culture biofilms are not well understood and were examined in this study. Staphylococcus aureus and Burkholderia cenocepacia, two common CF pathogens, were used …
Lipotoxin F Of Pseudomonas Aeruginosa Is An Algu-Dependent And Alginate-Independent Outer Membrane Protein Involved In Resistance To Oxidative Stress And Adhesion To A549 Human Lung Epithelia, F. Damron, Jennifer Napper, M. Teter, Hongwei Yu
Lipotoxin F Of Pseudomonas Aeruginosa Is An Algu-Dependent And Alginate-Independent Outer Membrane Protein Involved In Resistance To Oxidative Stress And Adhesion To A549 Human Lung Epithelia, F. Damron, Jennifer Napper, M. Teter, Hongwei Yu
Hongwei Yu
Chronic lung infection with P. aeruginosa and excessive neutrophil-associated inflammation are major causes of morbidity and mortality in patients with cystic fibrosis (CF). Overproduction of an exopolysaccharide known as alginate leads to the formation of mucoid biofilms that are resistant to antibiotics and host defences. Alginate overproduction or mucoidy is controlled by a stress-related ECF sigma factor AlgU/T. Mutation in the anti-sigma factor MucA is a known mechanism for conversion to mucoidy. Recently, we showed that inactivation of a kinase (KinB) in nonmucoid strain PAO1 results in overproduction of alginate. Here, we report the initial characterization of lipotoxin F (LptF, …
Inhibition Of Burkholderia Multivorans Adhesion To Lung Epithelial Cells By Bivalent Lactosides, Ciara Wight, Rosaria Leyden, Paul V. Murphy, Máire Callaghan, Trinidad Velasco-Torrijos, Siobhan Mcclean
Inhibition Of Burkholderia Multivorans Adhesion To Lung Epithelial Cells By Bivalent Lactosides, Ciara Wight, Rosaria Leyden, Paul V. Murphy, Máire Callaghan, Trinidad Velasco-Torrijos, Siobhan Mcclean
Articles
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. Development of therapies which can prevent or reduce the risk of colonization on exposure to Bcc in the environment would be a better alternative to antimicrobial agents. Previously, it has been shown that Bcc strains bound to many glycolipid receptors on lung epithelia. Using a …
Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole
Epoxide-Mediated Cifr Repression Of Cif Gene Expression Utilizes Two Binding Sites In Pseudomonas Aeruginosa, Alicia E. Ballok, Christopher D. Bahl, Emily L. Dolben, Allia K. Lindsay, Jessica D. St. Laurent, Deborah Hogan, Dean Madden, George A. O'Toole
Dartmouth Scholarship
Pseudomonas aeruginosa secretes an epoxide hydrolase virulence factor that reduces the apical membrane expression of ABC transporters such as the cystic fibrosis transmembrane conductance regulator (CFTR). This virulence factor, named CFTR inhibitory factor (Cif), is regulated by a TetR-family, epoxide-responsive repressor known as CifR via direct binding and repression. We identified two sites of CifR binding in the intergenic space between cifR and morB, the first gene in the operon containing the cif gene. We have mapped these binding sites and found they are 27 bp in length, and they overlap the -10 and +1 sites of both the cifR …
Bacterial Host Interactions In Cystic Fibrosis, Máire Callaghan, Siobhan Mcclean
Bacterial Host Interactions In Cystic Fibrosis, Máire Callaghan, Siobhan Mcclean
Articles
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). Successful dominant CF pathogens combine an effective arsenal to establish infection and counter-attack the host response, together with an ability to adapt readily to an unfavourable environment. Hypermutability is common among CF pathogens facilitating adaptation and as …
Activation Of Mmp-9 By Human Lung Epithelial Cells In Response To The Cystic Fibrosis-Associated Pathogen Burkholderia Cenocepacia Reduced Wound Healing In Vitro, Ciara Wright ], Ruth Pilkington, Máire Callaghan, Siobhan Mcclean
Activation Of Mmp-9 By Human Lung Epithelial Cells In Response To The Cystic Fibrosis-Associated Pathogen Burkholderia Cenocepacia Reduced Wound Healing In Vitro, Ciara Wright ], Ruth Pilkington, Máire Callaghan, Siobhan Mcclean
Articles
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. The aim of this work was to examine the role of MMPs in the pathogenesis of B. cepacia complex, which has not been explored to date. Real-time PCR analysis showed that B. cenocepacia infection upregulated MMP-2 and MMP-9 genes in the CF lung cell line CFBE41o- within 1 h, whereas MMP-2, -7, and -9 genes were upregulated in the non-CF lung cell line 16HBE14o-. Conditioned media from …
Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean
Virulence Of An Emerging Respiratory Pathogen, Genus Pandoraea, In Vivo And Its Interactions With Lung Epithelial Cells, Gillian Herbert, Anne Costello, Lydia Fabunmi, Kirsten Schaffer, Kevin Kavanagh, Emma M. Caraher, Máire Callaghan, Siobhan Mcclean
Articles
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. pulmonicola isolates and strains from other Pandoraea species. Three patients from whom the P. pulmonicola isolates were isolated have since died. The in vivo virulence of these and other Pandoraea strains was examined by determining the ability to kill Galleria mellonella larvae. The P. pulmonicola strains generally were the most virulent of the species tested, with three …
Real-Time Pcr Method For The Quantification Of Burkholderia Cepacia Complex Attached To Lung Epithelial Cells And Inhibitionn Of That Attachment, Ciara Wight, Gillian Herbert, Ruth Pilkington, Máire Callaghan, Siobhan Mcclean
Real-Time Pcr Method For The Quantification Of Burkholderia Cepacia Complex Attached To Lung Epithelial Cells And Inhibitionn Of That Attachment, Ciara Wight, Gillian Herbert, Ruth Pilkington, Máire Callaghan, Siobhan Mcclean
Articles
To develop a rapid method to quantify the attachment of the cystic fibrosis pathogen, Burkholderia multivorans, to lung epithelial cells (16HBE14o(-)) using real-time PCR with a view to monitoring potential inhibition of lung cell attachment. Mammalian and bacterial DNA were purified from bacteria attached to lung epithelial cells. The relative amount of bacteria attached was determined by amplification of the recA gene relative to the human GAPDH gene, in the presence of SYBR Green. The method was thoroughly validated and shown to correlate well with traditional plating techniques. Inhibition of bacterial attachment with simple sugars was then evaluated by real-time …