Innovative therapies against cystic fibrosis have shown promise for increasing the effectiveness of antibiotics in the treatment of chronic and acute bacterial respiratory infections in cystic fibrosis patients, and may also provide a model for potential HIV therapies in the future.

A number of compounds that block a key protein (exoenzymeS or ExoS) have been identified by Professor Igor Stagljar of the University of Toronto, with one—exosin—inhibiting infections in mammalian cells.

Past studies have shown it is possible to prevent or delay the onset of certain chronic or deadly infections in cystic fibrosis patients with early antibiotic treatment. But the current availability of antibiotics against Pseudomonas aeruginosa, a pathogen that can cause urinary tract infections, respiratory system infections, dermatitis, soft tissue infections, bacteremia, bone and joint infections, gastrointestinal infections and a variety of systemic infections, is limited and the pathogen shows signs of drug resistance.

In an article published in the journal PLoS Genetics, a team of investigators identified several drugs that block a Pseudomonas aeruginosa toxin called ExoS.

"These studies created a road map to the rational design of more potent, highly selective inhibitors against other similar toxins using a totally novel yeast-based approach," says lead author Stagljar. "This innovative approach is an important advance, not only for the value it may have in cystic fibrosis treatment, but also because this technique could be used to design novel therapies for any bacterial pathogen as well as the HIV virus."

Staglar’s next step is to test the action of their inhibitors in an animal model of cystic fibrosis, which if successful may provide a way for the treatment ofthis debilitating disease.
In the next phase of their research, Stagljar and his colleagues plan to test the action of their inhibitors in an animal model of cystic fibrosis. If successful, the therapeutics may provide an avenue for the treatment of this debilitating disease.

Source: University of Toronto