DOES LOW MAGNESIUM IN CYSTIC FIBROSIS CONTRIBUTE TO BACTERIAL PATHOGENICITY?

Abstract

Cystic fibrosis (CF) is a genetic disease for which there is currently no cure. Individuals with CF are plagued by myriad symptoms, including chronic pneumonia, which diminishes quality of life and reduces life expectancy to 40 years. The most common bacterium in CF patients’ lungs is Pseudomonas aeruginosa, a highly adaptable organism capable of surviving robust antibi-otic treatment. At the heart of developing improved treatments for CF pa-tients is the need to better understand P. aeruginosa pathogenicity. To this end, we have been studying the role of magnesium, which is often found at below normal levels in CF patients. Magnesium is an essential element in numerous cellular functions in both bacteria and humans. In previous re-search, we developed a P. aeruginosa strain with a deletion of the magnesi-um transport protein MgtE, as well as 16 plasmids carrying different muta-tions of the mgtE gene. Experiments with these constructs demonstrated a relationship between magnesium transport and bacterial toxin production. In the research presented here, we hypothesize that lower levels of magnesium may trigger a bacterial response, causing a change in P. aeruginosa patho-genicity. Changes may include differential growth, toxin release, and for-mation of biofilms, which are surface-adhered, antibiotic tolerant bacterial communities in a protective polysaccharide matrix. Using various magnesi-um levels, we have measured P. aeruginosa growth rates, motility, biofilm formation, and cytotoxicity toward cultured cells derived from the CF bron-chial epithelium. Preliminary results suggest that lower magnesium contrib-utes to changes in the bacterium that favor persistence in the CF lung. On-going studies include the effect of long-term growth of P. aeruginosa in low magnesium and how this impacts a number of virulence factors. We antici-pate that our research will elucidate the relationship between magnesium and P. aeruginosa pathogenicity and potentially lead to improved treatments for CF patients.