scholarly journals Alginate synthesis by Pseudomonas aeruginosa: a key pathogenic factor in chronic pulmonary infections of cystic fibrosis patients.

1991 ◽  
Vol 4 (2) ◽  
pp. 191-206 ◽  
Author(s):  
T B May ◽  
D Shinabarger ◽  
R Maharaj ◽  
J Kato ◽  
L Chu ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Biosynthetic Pathway ◽  
Pulmonary Infection ◽  
Regulatory Mechanism ◽  
Regulatory Proteins ◽  
Host Immune System ◽  
Pathogenic Factor ◽  
Pulmonary Infections

Pulmonary infection by mucoid, alginate-producing Pseudomonas aeruginosa is the leading cause of mortality among patients suffering from cystic fibrosis. Alginate-producing P. aeruginosa is uniquely associated with the environment of the cystic fibrosis-affected lung, where alginate is believed to increase resistance to both the host immune system and antibiotic therapy. Recent evidence indicates that P. aeruginosa is most resistant to antibiotics when the infecting cells are present as a biofilm, as they appear to be in the lungs of cystic fibrosis patients. Inhibition of the protective alginate barrier with nontoxic compounds targeted against alginate biosynthetic and regulatory proteins may prove useful in eradicating P. aeruginosa from this environment. Our research has dealt with elucidating the biosynthetic pathway and regulatory mechanism(s) responsible for alginate synthesis by P. aeruginosa. This review summarizes reports on the role of alginate in cystic fibrosis-associated pulmonary infections caused by P. aeruginosa and provides details about the biosynthesis and regulation of this exopolysaccharide.

scholarly journals Protection against Pulmonary Infection with Pseudomonas aeruginosa following Immunization with P. aeruginosa-Pulsed Dendritic Cells

2001 ◽  
Vol 69 (7) ◽  
pp. 4521-4527 ◽  
Author(s):  
Stefan Worgall ◽  
Toshiaki Kikuchi ◽  
Ravi Singh ◽  
Katherine Martushova ◽  
Leah Lande ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Dendritic Cells ◽  
Protective Immunity ◽  
Pulmonary Infection ◽  
Host Immune System ◽  
Pulmonary Infections ◽  
Murine Bone Marrow ◽  
Pulsed Dc

ABSTRACT To develop a Pseudomonas aeruginosa vaccine that allows the host immune system to select the antigens, we hypothesized that dendritic cells (DC) pulsed with P. aeruginosa would induce protective immunity against pulmonary infections with P. aeruginosa. Incubation of murine bone marrow-derived DC with P. aeruginosa in vitro led to uptake of P. aeruginosa and activation of the DC. Spleen-derived CD4+ cells from mice immunized withP. aeruginosa-pulsed DC showed increased proliferation, demonstrating that DC pulsed with P. aeruginosa were capable of eliciting a P. aeruginosa-specific immune response. To evaluate if P. aeruginosa-pulsed DC can induce protective immunity against P. aeruginosapulmonary infection, DC incubated with P. aeruginosa in vitro were administered systemically to syngeneic mice, and the mice were then challenged by intrapulmonary infection with P. aeruginosa (5 × 104 CFU/mouse) 13 days later. Unimmunized control mice and mice who had previously received naive DC or DC stimulated with lipopolysaccharide or Escherichia coli died within 72 h. In contrast, 45% of mice receivingP. aeruginosa-pulsed DC demonstrated prolonged survival (>14 days). Finally, DC-pulsed with heat-inactivated P. aeruginosa protected CD8−/− but not CD4−/− mice, demonstrating that CD4+ T cells were required for the DC pulsed with P. aeruginosa to induce protective immunity.

scholarly journals Porphyromonas, a potential predictive biomarker of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis

2019 ◽  
Vol 6 (1) ◽  
pp. e000374 ◽  
Author(s):  
Marlène Keravec ◽  
Jérôme Mounier ◽  
Charles-Antoine Guilloux ◽  
Marie-Sarah Fangous ◽  
Stanislas Mondot ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Pulmonary Infection ◽  
Predictive Biomarker ◽  
Early Years ◽  
Second Step ◽  
Pulmonary Infections ◽  
Prospective Multicentre Study ◽  
New Strategies

IntroductionPseudomonas aeruginosa pulmonary infections are the primary cause of morbi-mortality in patients with cystic fibrosis (CF). In this cohort study, the objective was to identify candidate biomarkers of P. aeruginosa infection within the airway microbiota.MethodsA 3-year prospective multicentre study (PYOMUCO study) was conducted in Western France and included patients initially P. aeruginosa free for at least 1 year. A 16S-targeted metagenomics approach was applied on iterative sputum samples of a first set of patients (n=33). The composition of airway microbiota was compared according to their P. aeruginosa status at the end of the follow-up (colonised vs non-colonised), and biomarkers associated with P. aeruginosa were screened. In a second step, the distribution of a candidate biomarker according to the two groups of patients was verified by qPCR on a second set of patients (n=52) coming from the same cohort and its load quantified throughout the follow-up.ResultsPorphyromonas (mainly P. catoniae) was found to be an enriched phylotype in patients uninfected by P. aeruginosa (p<0.001). This result was confirmed by quantitative PCR. Conversely, in patients who became P. aeruginosa-positive, P. catoniae significantly decreased before P. aeruginosa acquisition (p=0.014).DiscussionFurther studies on replication cohorts are needed to validate this potential predictive biomarker, which may be relevant for the follow-up in the early years of patients with CF. The identification of infection candidate biomarkers may offer new strategies for CF precision medicine.

scholarly journals Glucosylceramide Critically Contributes to the Host Defense of Cystic Fibrosis Lungs

2017 ◽  
Vol 41 (3) ◽  
pp. 1208-1218 ◽  
Author(s):  
Barbara Kovacic ◽  
Carolin Sehl ◽  
Barbara Wilker ◽  
Markus Kamler ◽  
Katrin Anne Becker ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Severe Pneumonia ◽  
Autosomal Recessive Disorder ◽  
Bactericidal Effect ◽  
Apical Surface ◽  
Pulmonary Infections

Background: Cystic fibrosis (CF) is the most common autosomal-recessive disorder in western countries. Previous studies have demonstrated an important role of sphingolipids in the pathophysiology of cystic fibrosis. It has been shown that ceramide has a central role in various pulmonary infections, including those with Pseudomonas aeruginosa (P. aeruginosa). Ceramide is accumulated in the airways of CF mice and patients. However, little is known about a potential role of glucosylceramide in cystic fibrosis. Methods: We investigated the expression of glucosylceramide and lactosylceramide in the respiratory tract of murine and human CF samples by immunohistochemistry and analyzed effects of glucosylceramide on P. aeruginosa in vitro. We performed pulmonary infections with P. aeruginosa and tested inhalation with glucosylceramide. Results: We demonstrate that glucosylceramide is down-regulated on the apical surface of bronchial and tracheal epithelial cells in cystic fibrosis mice. Although glucosylceramide did not have a direct bactericidal effect on Pseudomonas aeruginosa in vitro, inhalation of CF mice with glucosylceramide protected these mice from infection with P. aeruginosa, while non-inhaled CF mice developed severe pneumonia. Conclusion: Our data suggest that glucosylceramide acts in vivo in concert with ceramide and sphingosine to determine the pulmonary defense against P. aeruginosa.

Pulmonary infection of cystic fibrosis mice with Staphylococcus aureus requires expression of α-toxin

2018 ◽  
Vol 399 (10) ◽  
pp. 1203-1213 ◽  
Author(s):  
Simone Keitsch ◽  
Joachim Riethmüller ◽  
Matthias Soddemann ◽  
Carolin Sehl ◽  
Barbara Wilker ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Staphylococcus Aureus ◽  
Epithelial Cells ◽  
Pulmonary Infection ◽  
Severe Pneumonia ◽  
Pulmonary Infections ◽  
Acid Ceramidase ◽  
Bronchial Epithelial ◽  
Infection Susceptibility

Abstract Pulmonary infections of cystic fibrosis (CF) patients with Staphylococcus aureus (S. aureus) occur very early in the disease. The molecular details that cause infection-susceptibility of CF patients to and mediate infection with S. aureus are poorly characterized. Therefore, we aimed to identify the role of α-toxin, a major S. aureus toxin, for pulmonary infection of CF mice. Infection with S. aureus JE2 resulted in severe pneumonia in CF mice, while wildtype mice were almost unaffected. Deficiency of α-toxin in JE2-Δhla reduced the pathogenicity of S. aureus in CF mice. However, CF mice were still more susceptible to the mutant S. aureus strain than wildtype mice. The S. aureus JE2 induced a marked increase of ceramide and a downregulation of sphingosine and acid ceramidase expression in bronchi of CF mice. Deletion of α-toxin reduced these changes after infection of CF mice. Similar changes were observed in wildtype mice, but at much lower levels. Our data indicate that expression of α-toxin is a major factor causing S. aureus infections in CF mice. Wildtype S. aureus induces a marked increase of ceramide and a reduction of sphingosine and acid ceramidase expression in bronchial epithelial cells of wildtype and CF mice, changes that determine infection susceptibility.

scholarly journals Role of quorum sensing by Pseudomonas aeruginosa in microbial keratitis and cystic fibrosis

Microbiology ◽  
2008 ◽  
Vol 154 (8) ◽  
pp. 2184-2194 ◽  
Author(s):  
M. D. P. Willcox ◽  
H. Zhu ◽  
T. C. R. Conibear ◽  
E. B. H. Hume ◽  
M. Givskov ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Microbial Keratitis

scholarly journals EPS4.02 Porphyromonas, a candidate biomarker for detection of Pseudomonas aeruginosa pulmonary infection in cystic fibrosis

2018 ◽  
Vol 17 ◽  
pp. S43 ◽  
Author(s):  
C.-A. Guilloux ◽  
G. Marenne ◽  
S. Mondot ◽  
C. Lamoureux ◽  
L. Billard ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Pulmonary Infection

Characterization by pyocine typing and serotyping of oral and sputum strains of Pseudomonas aeruginosa isolated from cystic fibrosis patients

1987 ◽  
Vol 33 (3) ◽  
pp. 221-225 ◽  
Author(s):  
Kunio Komiyama ◽  
Brian F. Habbick ◽  
Tom Martin ◽  
Satwant K. Tumber
Keyword(s):  
Cystic Fibrosis ◽  
Pseudomonas Aeruginosa ◽  
Oral Cavity ◽  
Buccal Mucosa ◽  
Single Strain ◽  
Ecological Sites ◽  
Dental Plaques ◽  
Different Strains

Oral and sputum isolates of Pseudomonas aeruginosa in patients with cystic fibrosis were investigated. Of the 17 patients studied, 12 patients (71%) yielded both mucoid and nonmucoid variants of Pseudomonas aeruginosa from sputum and (or) various oral ecological sites, such as buccal mucosa, tongue dorsum, dental plaques, and saliva. A total of 51 strains of mucoid and nonmucoid Pseudomonas aeruginosa were isolated from these patients and were phenotypically characterized by both pyocine typing and serotyping. Five patients (42%) were colonized or infected by a single strain of Pseudomonas aeruginosa, whereas 7 patients (58%) were cocolonized or coinfected by two or more phenotypically different strains of Pseudomonas aeruginosa. To understand the mechanisms involved in Pseudomonas aeruginosa colonization, it may be necessary to identify multiple isolates of Pseudomonas aeruginosa not only from the sputum but also from the various oral ecological sites and to further explore the role of the oral cavity in this colonization.

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