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Full-Text Articles in Medicine and Health Sciences

Analysis Of The Pseudomonas Aeruginosa Regulon Controlled By The Sensor Kinase Kinb And Sigma Factor Rpon, F. Damron, Joshua Owings, Yuta Okkotsu, John Varga, Jill Schurr, Joanna Goldberg, Michael Schurr, Hongwei Yu Aug 2012

Analysis Of The Pseudomonas Aeruginosa Regulon Controlled By The Sensor Kinase Kinb And Sigma Factor Rpon, F. Damron, Joshua Owings, Yuta Okkotsu, John Varga, Jill Schurr, Joanna Goldberg, Michael Schurr, Hongwei Yu

Hongwei Yu

Alginate overproduction by P. aeruginosa, also known as mucoidy, is associated with chronic endobronchial infections in cystic fibrosis (CF). Alginate biosynthesis is initiated by the extracytoplasmic function sigma factor (σ(22), AlgU/T). In the wild type (wt) nonmucoid strains, such as PAO1, AlgU is sequestered to the cytoplasmic membrane by the anti-sigma factor MucA that inhibits alginate production. The mucA mutation that relieves AlgU from this sequestration is one mechanism underlying the conversion to mucoidy. However, the mucoid conversion can occur in wt mucA strains via the degradation of MucA by activated intramembrane proteases AlgW and/or MucP. Previously we reported that …


Defect In Early Lung Defence Against Pseudomonas Aeruginosa In Dba/2 Mice Is Associated With Acute Inflammatory Lung Injury And Reduced Bactericidal Activity In Naive Macrophages, Kari Wilson,, Jennifer Napper,, James Denvir, Vincent Sollars, Hongwei Yu Aug 2012

Defect In Early Lung Defence Against Pseudomonas Aeruginosa In Dba/2 Mice Is Associated With Acute Inflammatory Lung Injury And Reduced Bactericidal Activity In Naive Macrophages, Kari Wilson,, Jennifer Napper,, James Denvir, Vincent Sollars, Hongwei Yu

Hongwei Yu

Pseudomonas aeruginosa is an opportunistic pathogen that causes serious respiratory disease in the immune-compromised host. Using an aerosol infection model, 11 inbred mouse strains (129/Sv, A/J, BALB/c, C3H/HeN, C57BL/6, DBA/2, FVB, B10.D2/oSnJ, B10.D2/nSnJ, AKR/J and SWR/J) were tested for increased susceptibility to P. aeruginosa lung colonization. DBA/2 was the only mouse strain that had increased bacterial counts in the lung within 6 h post-infection. This deficiency incited a marked inflammatory response with reduced bacterial lung clearance and a mortality rate of 96.7 %. DBA/2 mice displayed progressive deterioration of lung pathology with extensive alveolar exudate and oedema formation at 48–72 …


Pseudomonas Aeruginosa Mucd Regulates The Alginate Pathway Through Activation Of Muca Degradation Via Mucp Proteolytic Activity, F. Damron, Hongwei Yu Aug 2012

Pseudomonas Aeruginosa Mucd Regulates The Alginate Pathway Through Activation Of Muca Degradation Via Mucp Proteolytic Activity, F. Damron, Hongwei Yu

Hongwei Yu

Alginate overproduction in Pseudomonas aeruginosa can be caused by the proteolysis of the anti-sigma factor MucA regulated by the AlgW protease. Here, we show that inactivation of MucD, an HtrA/DegP homolog and alginate regulator, can bypass AlgW, leading to an atypical proteolysis of MucA that is dependent on the MucP protease.


The Mycoplasma Genitalium Mg_454 Gene Product Resists Killing By Organic Hydroperoxides, Sankaralingam Saikolappan, Smitha Sasindran, Hongwei Yu, Joel Basema, Subramanian Dhandayuthapani Aug 2012

The Mycoplasma Genitalium Mg_454 Gene Product Resists Killing By Organic Hydroperoxides, Sankaralingam Saikolappan, Smitha Sasindran, Hongwei Yu, Joel Basema, Subramanian Dhandayuthapani

Hongwei Yu

Mycoplasma genitalium is the smallest self-replicating organism and a successful human pathogen associated with a range of genitourinary maladies. As a consequence of its restricted genome size, genes that are highly conserved in other bacteria are absent in M. genitalium. Significantly, genes that encode antioxidants like superoxide dismutase and catalase-peroxidase are lacking. Nevertheless, comparative genomics has revealed that MG_454 of M. genitalium encodes a protein with putative function as an organic hydroperoxide reductase (Ohr). In this study, we found that an M. genitalium transposon mutant that lacks expression of MG_454 was sensitive to killing by t-butyl hydroperoxide and cumene hydroperoxide. …


Regulated Proteolysis Controls Mucoid Conversion In Pseudomonas Aeruginosa, Dongru Qiu, Vonya Eisinger, Donald Rowen, Hongwei Yu Aug 2012

Regulated Proteolysis Controls Mucoid Conversion In Pseudomonas Aeruginosa, Dongru Qiu, Vonya Eisinger, Donald Rowen, Hongwei Yu

Hongwei Yu

Overproduction of the exopolysaccharide alginate causes mucoid conversion in Pseudomonas aeruginosa and is a poor prognosticator in cystic fibrosis. The ECF σ factor AlgU and its cognate anti-σ factor MucA are two principal regulators of alginate production. Here, we report the identification of three positive regulators of alginate biosynthesis: PA4033 (designated mucE), PA3649 (designated mucP), and algW. MucE, a small protein (9.5 kDa), was identified as part of a global mariner transposon screen for new regulators of alginate production. A transposon located in its promoter caused the overexpression of MucE and mucoid conversion in P. aeruginosa strains PAO1 and PA14. …


Persistent Infections And Immunity In Cystic Fibrosis, Hongwei Yu, Nathan Head Aug 2012

Persistent Infections And Immunity In Cystic Fibrosis, Hongwei Yu, Nathan Head

Hongwei Yu

Cystic fibrosis (CF) is the most common autosomal recessive lethal disease in the Caucasian population. Chronic respiratory infections with Pseudomonas aeruginosa, neutrophil-dominated airway inflammation and progressive lung damage are the major causes of morbidity and mortality in CF. Two persistent infection phenotypes expressed by this bacterium are biofilm and mucoidy. Biofilm, also called the microcolony mode of growth is the surface-associated adherent bacterial community, while mucoidy refers to a phenotype conducive to copious amounts of mucoid exopolysaccharide (MEP)/alginate that provides a matrix for mature biofilms conferring resistance to host defenses and antibiotics. Recent completion of the whole genomic sequence of …