Mohammad Tanha / Biology / Faculty Mentor: Mark Pellegrino
Bacteria manipulate host organelles to survive and infect the host. Pathogens often target mitochondria as they have essential functions. Cells initiate various recovery programs to repair damaged mitochondria during infection and other forms of stress. The mitochondrial unfolded protein response (UPRmt) regulates mitochondrial protective genes transcriptionally. The UPRmt in the model organism Caenorhabditis elegans controls an innate immune response that protects the host during infection. Our earlier findings suggest that Pseudomonas aeruginosa infection activates the UPRmt in C. elegans due to toxins targeting mitochondrial function. Intriguingly, the UPRmt is suppressed during prolonged infection. We found that the P. aeruginosa acyl-CoA dehydrogenase FadE2, which catabolizes branched-chain amino acids and fatty acids, is required for UPRmt suppression during P. aeruginosa infection. FadE2 is the only P. aeruginosa acyl-CoA dehydrogenase we found to suppress UPRmt. We hypothesized that perhaps FadE2 is preferentially activated during stress. Indeed, P. aeruginosa establishes itself in the intestinal lumen of C. elegans during infection, a hostile environment home to a variety of environmental stresses that the pathogen must mitigate. Consistently, we discovered that FadE2 contributes to pathogen survival specifically during oxidative stress. We present here preliminary findings suggesting that FadE2 may be regulated directly via an oxidative-medited mechanism.
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