Cystic Fibrosis

Microbiome Associations#

The CF lung harbors a polymicrobial community that evolves over the patient's lifetime. Pseudomonas aeruginosa—The dominant CF pathogen by adulthood; forms tenacious biofilms in the dehydrated mucus layer. Its siderophores pyoverdine and pyochelin aggressively scavenge iron from host transferrin and lactoferrin, providing the metabolic fuel for chronic colonization.

Staphylococcus aureus—Often dominates in childhood CF; uses different iron acquisition strategies (staphyloferrin, hemolysins) but occupies a similar ecological niche. Burkholderia cepacia complex—Opportunistic colonizer associated with rapid lung function decline; carries formidable siderophore systems.

Aspergillus—Fungal colonization is common; forms interkingdom biofilms with bacteria, providing Functional Shielding against host defenses.

The CF lung microbiome typically shows decreasing diversity over time, converging toward P. aeruginosa dominance as the organism adapts through mutations in iron regulation, quorum sensing, and mucoid phenotype conversion.

Metal Associations#

Iron ecology is the defining metal story in CF. Iron excess in CF airways—Thick, dehydrated mucus traps iron. Chronic Metal-Driven Inflammation releases iron from damaged tissue.

Repeated antibiotic courses kill commensals but leave iron available for resistant pathobionts.

Siderophore competition—P. aeruginosa produces two siderophores: pyoverdine (high-affinity iron(III) (Fe3+) chelator) and pyochelin (lower affinity but broader metal range). These directly compete with host Lactoferrin and Transferrin for iron—a canonical Siderophore Competition battleground.

PrrF sRNA iron regulation—P. aeruginosa uses PrrF small RNAs to coordinate iron metabolism, regulating iron storage proteins and peroxide resistance. Under iron limitation, PrrF represses iron-using pathways to conserve scarce iron; understanding this regulation is critical for anti-virulence drug development.^{[1]Ouattara 2025 — Iron and Peroxide Regulation of the PrrF sRNAs and a Conserved Dps-Like Protein in Pseudomonas aeruginosa and Pseudomonas fluorescensKhady O Ouattara, Amanda G Oglesby · 2025Open reference 1 ↓}

Zinc starvation as host defense—The host deploys nutritional immunity by restricting zinc availability in CF airways via calprotectin. P. aeruginosa responds by upregulating zinc import systems (znuABC) and producing the metallophore pseudopaline (zrmABCD).^{[2]Michetti 2025 — Modelling Host-Pathogen Interactions: Galleria mellonella as a Platform to Study Pseudomonas aeruginosa Response to Host-Imposed Zinc StarvationEmma Michetti, Tulasi Abinya Mandava, Valerio Secli et al. · 2025Open reference 2 ↓}