Princeton University Library Catalog
- Tso, William WeiKang [Browse]
- Senior thesis
- Brynildsen, Mark P. [Browse]
- Princeton University. Department of Chemical and Biological Engineering [Browse]
- Class year:
- 54 pages
- Summary note:
- Nitric oxide (NO•) plays an integral role in the host-pathogen relationship. Host
immune cells generate NO• to prevent bacterial virulence, but pathogens have evolved
NO• detoxification enzymes to thwart their effectiveness. One consequence of NO• stress
for pathogens is the inability to synthesize amino acids, leading to inhibited growth.
Previous studies demonstrated that the addition of amino acids to the extracellular media
alleviated NO• mediated growth inhibition. We theorized that the presence of amino
acids could also improve NO• detoxification through facilitating the production of
relevant detoxification enzymes.
Using Escherichia coli as our model bacteria, we discovered that amino acid
supplementation instead inexplicably suppressed NO• detoxification. Experimental and
computational approaches revealed that Hmp, the predominant aerobic NO•
detoxification enzyme in E. coli, was not compromised in its catalytic ability, but its
synthesis under NO• stress was inhibited by the inclusion of amino acids in the
extracellular media. Quantification of mRNA production from the hmp promoter
following NO• treatment suggested that a transcriptional defect caused by the presence of
amino acids may be contributing to the inhibition of Hmp synthesis.