CFTR inhibitory factor

CFTR Inhibitory Factor (Cif) is a virulence factor produced by certain bacteria, including Pseudomonas aeruginosa. It plays a significant role in the pathogenesis of bacterial infections, particularly in patients with Cystic Fibrosis (CF). Cif is known to inhibit the function of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, which is crucial for chloride and bicarbonate ion transport in epithelial cells. The inhibition of CFTR by Cif leads to a decrease in airway surface liquid hydration and impairs mucociliary clearance, contributing to the accumulation of thick, sticky mucus in the lungs, a hallmark of CF.

Mechanism of Action

Cif exerts its effect by reducing the abundance of CFTR at the cell surface. It is believed to do this through a mechanism involving the reduction of CFTR mRNA levels, leading to decreased protein synthesis, and by increasing the degradation of CFTR protein through the lysosomal pathway. This dual action significantly diminishes the function of CFTR channels, affecting ion and water transport across the epithelial cell surface and leading to the characteristic thick mucus observed in CF patients.

Clinical Significance

The presence of Cif-producing Pseudomonas aeruginosa in the lungs of CF patients is associated with a more severe disease progression. The inhibition of CFTR by Cif not only exacerbates the symptoms of CF but also contributes to the establishment of chronic bacterial infections. These infections are difficult to treat due to the protective environment provided by the thick mucus and the inherent resistance of Pseudomonas aeruginosa to many antibiotics.

Research and Therapeutic Implications

Understanding the role of Cif in CF has opened new avenues for research and therapy development. Efforts are being made to develop inhibitors of Cif as a therapeutic strategy to restore CFTR function in CF patients infected with Cif-producing bacteria. Additionally, research into the molecular mechanisms of Cif action may provide insights into the broader understanding of CFTR regulation and the pathogenesis of CF.

See Also

• Cystic Fibrosis
• Pseudomonas aeruginosa
• Cystic Fibrosis Transmembrane Conductance Regulator
• Mucociliary clearance

NIH genetic and rare disease info

• NIH info on CFTR inhibitory factor

CFTR inhibitory factor is a rare disease.