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Iron bioavailability regulates Pseudomonas aeruginosa interspecies interactions through type VI secretion expression
Allison L Haas1, Anna C Zemke2, Jeffrey A Melvin1
1Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15219, USA.
Abstract:
The cystic fibrosis (CF) respiratory tract harbors pathogenic bacteria that cause life-threatening chronic infections. Of these, Pseudomonas aeruginosa becomes increasingly dominant with age and is associated with worsening lung function and declining microbial diversity. We aimed to understand why P. aeruginosa dominates over other pathogens to cause worsening disease. Here, we show that P. aeruginosa responds to dynamic changes in iron concentration, often associated with viral infection and pulmonary exacerbations, to become more competitive via expression of the TseT toxic effector. However, this behavior can be therapeutically targeted using the iron chelator deferiprone to block TseT expression and competition. Overall, we find that iron concentration and TseT expression significantly correlate with microbial diversity in the respiratory tract of people with CF. These findings improve our understanding of how P. aeruginosa becomes increasingly dominant with age in people with CF and provide a therapeutically targetable pathway to help prevent this shift.
Insights
Pseudomonas aeruginosa dominates in cystic fibrosis lungs by using iron to express a toxin. Iron chelators like deferiprone can block this, offering a new therapeutic target to improve lung health.
Area of Science:
- Microbiology
- Pulmonology
- Infectious Diseases
Background:
- Cystic fibrosis (CF) patients experience chronic respiratory infections.
- Pseudomonas aeruginosa (P. aeruginosa) increasingly dominates CF lung microbiota with age, correlating with disease progression.
- Understanding P. aeruginosa dominance is crucial for developing effective CF therapies.
Purpose of the Study:
- To investigate the mechanisms behind P. aeruginosa's dominance in the CF respiratory tract.
- To identify factors influencing P. aeruginosa's competitive advantage.
- To explore potential therapeutic targets to mitigate P. aeruginosa overgrowth.
Main Methods:
- Analysis of bacterial competition in dynamic iron concentrations relevant to CF exacerbations.
- Investigating the role of the TseT toxic effector in P. aeruginosa competitiveness.
- Correlating iron levels and TseT expression with microbial diversity in CF patient samples.
Main Results:
- P. aeruginosa utilizes dynamic iron availability to enhance competitiveness through TseT effector expression.
- Iron chelation therapy with deferiprone effectively inhibits TseT expression and P. aeruginosa competition.
- Iron concentration and TseT expression are significantly linked to reduced microbial diversity in CF lungs.
Conclusions:
- Iron-mediated TseT expression is a key driver of P. aeruginosa dominance in CF airways.
- Targeting iron metabolism with chelators like deferiprone presents a viable therapeutic strategy.
- Modulating iron and TseT offers a pathway to restore microbial balance and improve CF lung health.
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