Detection of conversion to mucoidy in Pseudomonas aeruginosa infecting cystic fibrosis patients

US6426187B1 · kind B1 · utility

Assignee

• The Board of Regents of the University of Texas System · US

Inventors

• Vojo P. Deretic · Bernalillo, US
• Daniel W. Martin · Carthage, US

Key dates

• Filing date: Jun 30, 2000
• Grant date: Jul 30, 2002
• Expiry date: Jun 30, 2020

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12Q2600/158
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Compositions and methods for detecting the conversion to mucoidy in Pseudomonas aeruginosa are disclosed. Chronic respiratory infections with mucoid Pseudomonas aeruginosa are the leading cause of high mortality and morbidity in cystic fibrosis. The initially colonizing strains are nonmucoid but in the cystic fibrosis lung they invariably convert into the mucoid form causing further disease deterioration and poor prognosis. Mucoidy is a critical P. aeruginosa virulence factor in cystic fibrosis that has been associated with biofilm develoment and resistance to phagocytosis. The molecular basis of this conversion to mucoidy is also disclosed. The present invention provides for detecting the switch from nonmucoid to mucoid state as caused by either frameshift deletions and duplications or nonsense changes in the second gene of the cluster, mucA. Inactivation of mucA results in constitutive expression of genes, such as algD, dependent on algU for transcription. Also disclosed is a novel alginate biosynthesis heterologous expression system for use in screening candidate substances that inhibit conversion to mucoidy.