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B.S., University of Oklahoma, Norman, OK, 2011
Honors and Awards:
Bacteria adapt to their environments through regulatory systems, genetic exchange, and mutations. Pseudomonas aeruginosa is exceptional at adaptation, especially in the airways of cystic fibrosis (CF) patients, using all three mechanisms when confronted with the barrage of antibiotics prescribed to the patients and the immune system of the host. We have discovered three clinical isolates taken from different CF patients that have the exact same 11 bp deletion in aguA, and two more isolates from patients at a different CF center also with a mutation in aguA. This gene encodes the agmatine deiminase for breaking down agmatine, a polycationic molecule at pH 7. Current literature shows that postively and negatively charges molecules, such as divalent cations and DNA, respectively, can alter antibiotic resistance and bacterial killing mediated through host defensins. I hypothesized that this mutation affords some protection against cationic antibiotics, such as aminoglycosides and polymyxins, and also causes interference with TLR4 signalling in macrophages due to the excess agmatine being pushed out into the extracellular space creating a less penetrable outermembrane for the cells.
Dalluge, JJ, JL McCurtain, AJ Gilbertsen, KA Kalstabakken and BJ Williams. May 10, 2015. Determination of Amgatine Using Isotope Dilution UPLC-Tandem Mass Spectrometry: Application to the Characterization of the Arginine Decarboxylase Pathway in Pseudomonas aeruginosa. Analytical and Bioanalytical Chemistry.