University of Minnesota
MICaB Graduate Program
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McCurtain
Jennifer McCurtain

E-mail:mccur023@umn.edu

Thesis Advisor: Ryan Hunter and Gary Dunny

Year entered: 2011

Degrees received:
B.S., University of Oklahoma, Norman, OK, 2011

Honors and Awards:

  • NHLBI T32 Training Grant Recipient (2012-present)
  • MICaB Travel Award, Spring 2017


Thesis research:
Pseudomonas aeruginosa is the most notorious microbe associated with the disorder cystic fibrosis (CF), and it often undergoes mutation events that can be advantageous while colonizing the CF airways. We have discovered ~5% of P. aeruginosa CF isolated harbor deletion mutations in the gene augA that encodes agmatine deiminase, required for breaking down agmatine in the arginine decarboxylase pathway. This causes agmatine, a cationic molecule, to accumulate both within and outside the cell. I wanted to know what advantage these deletion mutations and the resulting buildup of agmatine provide for the bacterium. The accumulation of agmatine increases the isolates' resistance to cationic antibiotics (aminoglycosides and polymyxins), but has no effect on bilfilm formation.

Preliminary studies indicate that agmatine masks the presence of LPS (lipopolysaccharide) from the host. This is suggested by a decrease in neutrophil recruitment using a mouse model of acute pneumonia when inoculated with the aguA deletion mutant compared to its aguA complement. Initial experiments using epithelial cell cultures showed reduced cytokine response to LPS in the presence of higher, but physiologically relevant, concentrations of agmatine. The reduction in IL-8 production corroborates the mouse neutrophil recruitment data. These deletion mutation, and the resulting accumulation of agmatine, could be a selective advantage for P. aeruginosa isolates colonizing the CF airways.

Publications:

  • 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.