Drug Could Potentially Address Staphylococcus Aureus Infections in CF
A new study entitled “Counteracting suppression of CFTR and voltage-gated K+ channels by a bacterial pathogenic factor with the natural product tannic acid” published in Elife reports on the discovery of an inhibitor for Staphylococcus aureus, the leading agent of infections in Cystic Fibrosis patients.
Cystic Fibrosis (CF) is caused by mutations in the Cftr gene (short for cystic fibrosis transmembrane conductance regulator). The CFTR protein is responsible for transport of chloride and sodium ions in and out of lung and intestinal epithelium cells. In the absence of functional CFTR protein, thick mucus accumulates, leaving CF patients more susceptible to infections.
One of the most common organisms causing early lung infections in CF patients is Staphylococcus aureus. These bacteria secrete an enzyme — sphingomyelinase C (SMase C) – which catalyzes the breakdown of sphingomyelin (a type of sphingolipid) in its two components, phosphocholine and ceramide. Notably, by targeting sphingomyelin that surrounds the CFTR protein, SMase C has an impact on CFTR activity. Thus, Staphylococcus aureus infections worsen CF patients’ symptoms by further decreasing any residual functional CFTR protein. Moreover, SMase C was shown to impair the function of lymphocytes (important mediators of immune responses) by inhibiting the flow of potassium ions in these cells.
In this study, a team of scientists from the University of Pennsylvania School of Medicine and the Howard Hughes Medical Institute discovered that the enzyme SMase C remains active and fully functional for long periods of time, even when the source bacteria were already killed. The authors hypothesized that targeting SMAse C would thus benefit CF patients’ outcomes, and so they screened a naturally-occurring library of more than 2,000 compounds that were previously approved for human use. They found one compound — tannic acid — could block SMAse C inhibitory effect on both CFTR and potassium channel protein. Since SMAse C is produced by other bacteria, the combined treatment of antibiotics and tannic acid is therefore, a promising new treatment for SMAse C releasing bacteria infections and, particularly important to CF patients.
This new research into combating new bacterial infections such as Staphylococcus aureus joins recent studies reported on in August about how targeted bacterial testing could decrease premature death in CF patients, particularly in the wake of increasing antibiotic resistance.