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Browsing by Subject "Cystic fibrosis (CF)"
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Item DOES LOW MAGNESIUM IN CYSTIC FIBROSIS CONTRIBUTE TO BACTERIAL PATHOGENICITY?(2012-04-13) Coffey, Barbara M.; Anderson, Gregory G.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.Item THE EFFECTS OF QUORUM SENSING ANTAGONISTS ON BIOFILM(Office of the Vice Chancellor for Research, 2012-04-13) Guzman, Juan M.; Anderson, Gregory G.Cystic fibrosis (CF) is a recessive genetic disorder that causes the for-mation of thick mucus plugs in the lungs of approximately 30,000 people in the United States and 60,000 individuals world-wide. Pseudomonas aeruginosa, an opportunistic bacterial pathogen, is able to colonize the mu-cus plugs and form antibiotic resistant biofilms. These microbial colonies, known as biofilms, cause serious problems for individuals living with CF. P. aeruginosa biofilms are able to cause chronic infections in the lungs of CF patients leading to increased morbidity and mortality. Using a modified bio-film assay, we tested the effects of modified chemical compounds and amino acids on P. aeruginosa biofilm dispersion. A previous study performed on P. aeruginosa, found that treatment of d- and l- amino acids resulted in biofilm dissemination. Through additional experiments, we will identify modified chemical compounds that induce biofilm dispersion. This research will in-crease our knowledge of P. aeruginosa biofilm dispersion, and allow us to explore new forms of treatment and therapy for CF patients with chronic in-fections that could be life threatening.Item Strategies for management of pediatric cystic fibrosis liver disease(Wiley, 2013-10-30) Bozic, Molly; Molleston, Jean; Pediatrics, School of Medicine