Related Experiment Video
Updated: Jan 12, 2026
A Fluorescence-based Method to Study Bacterial Gene Regulation in Infected Tissues
Published on: February 19, 2019
Functional CFTR may be required for Prevotella melaninogenica regulation of epithelial cell defense against
Maksym Goryachok1, Ana Fairbanks-Mahnke1, Sam Fulte1
1University of Colorado School of Medicine, Department of Otolaryngology - Head & Neck Surgery, Aurora, CO, USA.
Background:
Prevotella melaninogenica is enriched in the lungs of people with cystic fibrosis (pwCF), yet its functional impact on respiratory tract homeostasis remains incompletely understood. Prior studies identified immune modulatory effects following lung exposure to Prevotella, but the relevance of these findings for CF infections is unknown.
Methods:
The impact of P. melaninogenica on infection with the CF pathogen Staphylococcus aureus was evaluated using a mouse lung infection model and by measuring S. aureus adherence to human respiratory tract cystic fibrosis transmembrane conductance regulator (CFTR) mutant and isogenic wild-type (WT)-corrected CFBE41o- epithelial cells. Epithelial cytokine/chemokine secretion and RNA-sequencing were performed to compare P. melaninogenica-induced signaling programs in WT-corrected versus CFTR mutant cells.
Results:
P. melaninogenica significantly reduced S. aureus lung infection, associated with elevated S. aureus killing by lung neutrophils and impaired S. aureus adherence to epithelial cells. Live or killed P. melaninogenica were sufficient to mediate these effects, which were dependent on TLR2. P. melaninogenica impairment of S. aureus adherence required functional CFTR, as this effect was lost in CFTR mutant cells but restored by CFTR modulators. RNA-sequencing identified several antibacterial defense pathways selectively upregulated by P. melaninogenica in WT corrected epithelial cells, correlating with higher IL-8 and IL-6 cytokine production.
Conclusions:
P. melaninogenica enhanced neutrophil and epithelial defense against S. aureus, but the benefits of epithelial cell regulation by P. melaninogenica were lost with CFTR dysfunction. CFTR modulators rescued P. melaninogenica responsiveness in epithelial cells, highlighting the potential for synergistic effects of host-microbiome interactions and CFTR targeted therapies.
Insights
Prevotella melaninogenica enhances defenses against Staphylococcus aureus lung infections in cystic fibrosis (CF) models. However, these benefits are lost with CFTR dysfunction, though CFTR modulators can restore them.
Area of Science:
- Microbiology
- Immunology
- Pulmonary Medicine
Background:
- Prevotella melaninogenica is prevalent in cystic fibrosis (CF) lungs, but its role in respiratory health is unclear.
- Previous research suggested Prevotella modulates immune responses, but relevance to CF infections was unknown.
Purpose of the Study:
- To investigate the impact of P. melaninogenica on Staphylococcus aureus infection in CF models.
- To determine the role of cystic fibrosis transmembrane conductance regulator (CFTR) in P. melaninogenica-mediated host defense.
Main Methods:
- A mouse lung infection model was used to assess P. melaninogenica's effect on S. aureus.
- S. aureus adherence to CFTR-mutant and wild-type epithelial cells was measured.
- Epithelial cytokine secretion and RNA sequencing were performed.
Main Results:
- P. melaninogenica reduced S. aureus lung infection, enhanced neutrophil killing, and impaired bacterial adherence.
- These effects were TLR2-dependent and required functional CFTR for epithelial adherence.
- CFTR modulators restored P. melaninogenica's beneficial effects on epithelial cells.
Conclusions:
- P. melaninogenica boosts neutrophil and epithelial defenses against S. aureus.
- CFTR dysfunction negates epithelial benefits, but CFTR modulators can restore them.
- Synergistic host-microbiome and CFTR-targeted therapies show potential for CF treatment.
Related Concept Videos
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...
01:18Surface Membrane Barriers
The outer layer of the skin, the epidermis, is a robust barrier comprising layers of closely packed keratinized cells. This dense arrangement prevents microbes from penetrating the body. The periodic shedding of epidermal cells...
01:26Defense Mechanism Against Infection
In addition, many body organ systems have unique defenses against infection. The skin is an intact, multilayered surface preventing invasion by microorganisms unless impaired. Mucous membranes lining the mouth, nose, and eyelids are barriers...
01:28Gene Regulation in Microbial Communities: Quorum Sensing
01:23Cystic Fibrosis: Pathogenesis
CF is primarily caused by a genetic mutation in a chromosome 7 gene coding for the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The most common gene mutation leading to CF is the ΔF508 mutation,...
01:24Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors