Detection of conversion to mucoidy in pseudomonas aeruginosa inf

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

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536 2432, 435875, C07H 2104

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055918387

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. The molecular basis of this conversion to mucoidy is also disclosed. The algU gene encodes a protein homologous to an alternative sigma factor regulating sporulation and other developmental processes in Bacillus, and along with the negative regulators mucA and mucB comprises the gene cluster controlling conversion to mucoidy. The switch from nonmucoid to mucoid state is caused by frameshift deletions and duplications 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. Insertional inactivation of mucB on the chromosome of the standard genetic strain PAO also resulted in mucoid phenotype, and in a strong transcriptional activation of algD. Activation of algD results in increased synthesis of the exopolysaccharide alginate rendering P. aeruginosaa mucoid.

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