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Full-Text Articles in Medicine and Health Sciences
Pharmacological Modulation Of Cgmp Levels By Phosphodiesterase 5 Inhibitors As A Therapeutic Strategy For Treatment Of Respiratory Pathology In Cystic Fibrosis., Hongwei Yu, Jens Poschet, Graham Timmons, Jennifer Taylor-Cousar, Wojciech Ornatowski, Joseph Fazio, Elizabeth Perkett, Kari Wilson, Hugo De Jonge, Vojo Deretic
Pharmacological Modulation Of Cgmp Levels By Phosphodiesterase 5 Inhibitors As A Therapeutic Strategy For Treatment Of Respiratory Pathology In Cystic Fibrosis., Hongwei Yu, Jens Poschet, Graham Timmons, Jennifer Taylor-Cousar, Wojciech Ornatowski, Joseph Fazio, Elizabeth Perkett, Kari Wilson, Hugo De Jonge, Vojo Deretic
Hongwei Yu
The CFTR gene encodes a chloride channel with pleiotropic effects on cell physiology and metabolism. Here, we show that increasing cGMP levels to inhibit epithelial Na(+) channel in cystic fibrosis (CF) respiratory epithelial cells corrects several aspects of the downstream pathology in CF. Cell culture models, using a range of CF cell lines and primary cells, showed that complementary pharmacological approaches to increasing intracellular cGMP, by elevating guanyl cyclase activity though reduced nitric oxide, addition of cell-permeable cGMP analogs, or inhibition of phosphodiesterase 5 corrected multiple aspects of the CF pathological cascade. These included correction of defective protein glycosylation, bacterial …
Vanadate And Triclosan Synergistically Induce Alginate Production By Pseudomonas Aeruginosa Strain Pao1, F. Damron, Michael Davis, T. Withers, Robert Ernst, Joanna Goldberg, Guangli Yu, Hongwei Yu
Vanadate And Triclosan Synergistically Induce Alginate Production By Pseudomonas Aeruginosa Strain Pao1, F. Damron, Michael Davis, T. Withers, Robert Ernst, Joanna Goldberg, Guangli Yu, Hongwei Yu
Hongwei Yu
Alginate overproduction by P. aeruginosa strains, also known as mucoidy, is associated with chronic lung infections in cystic fibrosis (CF). It is not clear how alginate induction occurs in the wild-type (wt) mucA strains. When grown on Pseudomonas isolation agar (PIA), P. aeruginosa strains PAO1 and PA14 are non-mucoid, producing minimal amounts of alginate. Here we report the addition of ammonium metavanadate (AMV), a phosphatase inhibitor, to PIA (PIA-AMV) induced mucoidy in both these laboratory strains and early lung colonizing non-mucoid isolates with a wt mucA. This phenotypic switch was reversible depending on the availability of vanadate salts and triclosan, …
Cross-Sectional Analysis Of Clinical And Environmental Isolates Of Pseudomonas Aeruginosa: Biofilm Formation, Virulence, And Genome Diversity, Nathan Head, Hongwei Yu
Cross-Sectional Analysis Of Clinical And Environmental Isolates Of Pseudomonas Aeruginosa: Biofilm Formation, Virulence, And Genome Diversity, Nathan Head, Hongwei Yu
Hongwei Yu
Chronic lung infections with Pseudomonas aeruginosa biofilms are associated with refractory and fatal pneumonia in cystic fibrosis (CF). In this study, a group of genomically diverse P. aeruginosa isolates were compared with the reference strain PAO1 to assess the roles of motility, twitching, growth rate, and overproduction of a capsular polysaccharide (alginate) in biofilm formation. In an in vitro biofilm assay system, P. aeruginosa displayed strain-specific biofilm formation that was not solely dependent on these parameters. Compared with non-CF isolates, CF isolates expressed two opposing growth modes: reduced planktonic growth versus efficient biofilm formation. Planktonic cells of CF isolates showed …
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, …
The Pseudomonas Aeruginosa Sensor Kinase Kinb Negatively Controls Alginate Production Through Algw-Dependent Muca Proteolysis, Hongwei Yu, F. Damron, Dongru Qiu
The Pseudomonas Aeruginosa Sensor Kinase Kinb Negatively Controls Alginate Production Through Algw-Dependent Muca Proteolysis, Hongwei Yu, F. Damron, Dongru Qiu
Hongwei Yu
Mucoidy, or overproduction of the exopolysaccharide known as alginate, in Pseudomonas aeruginosa is a poor prognosticator for lung infections in cystic fibrosis. Mutation of the anti-sigma factor MucA is a well-accepted mechanism for mucoid conversion. However, certain clinical mucoid strains of P. aeruginosa have a wild-type (wt) mucA. Here, we describe a loss-of-function mutation in kinB that causes overproduction of alginate in the wt mucA strain PAO1. KinB is the cognate histidine kinase for the transcriptional activator AlgB. Increased alginate production due to inactivation of kinB was correlated with high expression at the alginate-related promoters P(algU) and P(algD). Deletion of …