Microbial Interactions in Cystic Fibrosis Pathogenesis

Cystic fibrosis (CF) lung disease is driven not only by the host genetics and immune response but by a dynamic microbial ecosystem in which bacteria, fungi and viruses engage in cooperative and antagonistic partnerships. Central among these are Pseudomonas aeruginosa and Aspergillus fumigatus, whose interkingdom interactions shape biofilm architecture, nutrient competition and virulence factor expression. Phage elements can mediate horizontal gene transfer, while small-molecule cues such as phenazines, homoserine lactones and siderophores govern redox balance and iron availability. Polymicrobial biofilms within the thickened mucus of CF airways display emergent properties that enhance antimicrobial tolerance and modulate host inflammation. Understanding these cross-kingdom dialogues has opened new avenues for anti-biofilm therapies, modulation of microbial signalling and precision management of chronic lung infection.

Research from Nature Portfolio

Studies have illuminated how bacterial secondary metabolites orchestrate both inhibitory and stimulatory effects on fungal partners. Work in a foundational report demonstrated that P. aeruginosa phenazine compounds exert dual functions: at high concentrations they generate reactive oxygen and nitrogen species that damage fungal cells, whereas at sub-inhibitory levels they facilitate iron uptake by A. fumigatus, promoting fungal growth. This mechanistic insight into redox modulation and iron chelation highlights a finely balanced antagonism that underpins persistent coinfections and suggests that targeting phenazine biosynthesis may rebalance microbial communities in CF airways.

Microbial Interactions in Cystic Fibrosis Pathogenesis publication trend

The graph below shows the total number of articles in microbial interactions in cystic fibrosis pathogenesis across all publications each year (not limited to Nature Index journals).

Technical terms

Biofilm: A structured microbial community embedded in an extracellular matrix that confers protection against antibiotics and host defences.

Phenazine: Redox-active secondary metabolites secreted by P. aeruginosa that modulate microbial competition and iron acquisition.

Quorum sensing: Cell-to-cell communication via diffusible signal molecules that synchronise gene expression across a microbial population.

Siderophore: High-affinity iron-chelating compounds secreted by microbes to scavenge iron from the environment or host.

Prophage: A latent bacteriophage genome integrated into the bacterial chromosome that can transfer genetic material and influence host physiology.

References

1. Filamentous prophage Pf4 promotes genetic exchange in Pseudomonas aeruginosa. The ISME Journal: Multidisciplinary Journal of Microbial Ecology (2024).
2. Co-assembling living material as an in vitro lung epithelial infection model. Matter (2024).
3. The Deciphering of Growth-Dependent Strategies for Quorum-Sensing Networks in Pseudomonas aeruginosa. Microorganisms (2023).
4. Interactions between Bacteria and Aspergillus fumigatus in Airways: From the Mycobiome to Molecular Interactions. Journal of Fungi (2023).
5. Pseudomonas aeruginosa manipulates redox and iron homeostasis of its microbiota partner Aspergillus fumigatus via phenazines. Scientific Reports (2015).