A 12 year old boy has a productive cough characterized by large volumes of foul-smelling sputum. Three years ago, the patient was diagnosed with pancreatic insufficiency, as evidenced by repetitive gastrointestinal symptoms of steatorrhea. After culture of the sputum, colorless, oxidase-positive colonies with a fruity aroma develop on the agar. The function of which of the following proteins is most likely inhibited by the bacteria responsible for this boy’s infection?
Correct Answer: A GTP-binding protein involved in the elongation step of protein synthesis
Description: The boy is displaying the characteristic symptoms of cystic fibrosis with bronchiectasis (accounting for the foul-smelling sputum) and pancreatic insufficiency, producing steatorrhea. However, the question directly relates to the infectious agent causing the pneumonia, Pseudomonas aeruginosa, an oxidase-positive bacteria with a fruity aroma. P. aeruginosa is a strictly aerobic gram-negative rod that produces an exotoxin (exotoxin A) that ADP-ribosylates, and therefore inhibits, eukaryotic elongation factor 2 (eEF-2), which is a G-protein involved in the eukaryotic translation of proteins. The cystic fibrosis transmembrane conduction regulator (CFTR) protein is the product of the cystic fibrosis gene, a large 24 exon gene located on the long arm of chromosome 7 (7q31). This protein has two nucleotide binding domains. In 70% of the families with the disease, a three base pair deletion at codon 508 of exon 10 results in the deletion of a phenylalanine (DF508). This codon is critical for one of the nucleotide binding sites of the CF gene product, resulting in poor channel in the apical membrane of epithelial cells. The defective chloride channel leads to impaired secretion of chloride in the lumen and promotes the absorption of sodium inside the cells. Water follows, concentrating the airway secretions. The increased viscosity of the airway secretions predisposes the patient to repeated infections. A GTP-binding protein similar to the one coupled with & alpha;2-adrenergic receptors refers to a G-protein that inhibits adenylate cyclase, lowering cAMP. This G-protein is sensitive to Peussis toxin. A GTP-binding protein similar to the one coupled with & beta;-adrenergic receptors refers to a G-protein that stimulates adenylate cyclase, increasing cAMP. This G-protein is sensitive to cholera toxin. Ref: Brooks G.F. (2013). Chapter 16. Pseudomonads, Acinetobacters, and Uncommon Gram-Negative Bacteria. In G.F. Brooks (Ed), Jawetz, Melnick, & Adelberg's Medical Microbiology, 26e.
Category:
Microbiology
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