FIGURE SUMMARY
Title

Identification of Potential Sepsis Therapeutic Drugs Using a Zebrafish Rapid Screening Approach

Authors
Widder, M., Carbaugh, C., van der Schalie, W., Miller, R., Brennan, L., Moore, A., Campbell, R., Akers, K., Ressner, R., Martin, M., Madejczyk, M., Dancy, B., Lee, P., Lanteri, C.
Source
Full text @ Life (Basel)
Figure 1

Caudal fin morphology of 3 dpf zebrafish. (A) Normal of caudal fin of control fish with no LPS exposure. (B) Caudal fin after 24 h of 60 µg/mL of P. aeruginosa LPS resulting in a tail edema and vascular leakage.
Figure 2 Bottom

Dose response curves for 3 dpf zebrafish (top graph) and 5 dpf zebrafish (bottom graph) for 24-h exposures to LPS derived from E. coli 0111:B4, P. aeruginosa, and K. pneumoniae.
Figure 2 Top

Dose response curves for 3 dpf zebrafish (top graph) and 5 dpf zebrafish (bottom graph) for 24-h exposures to LPS derived from E. coli 0111:B4, P. aeruginosa, and K. pneumoniae.
Figure 3

LPS concentration response curves for replicate tests during the optimization phase of assay development. The left graph depicts the percentage of fish with tail edema in response to increasing P. aeruginosa LPS concentrations. The right graph depicts the number of dead fish in response to increasing P. aeruginosa LPS concentrations. The goal was to determine a concentration that yielded close to 50% mortality while eliciting 100% combined tail edema and mortality in all fish. A concentration of 60 µg/mL of P. aeruginosa LPS was chosen for use in follow-on chemical screening.
Figure 4

Example of the rescue results from the initial drug screening from a single 96-well plate. Tegaserod showed complete rescue from LPS-induced tail and edema and mortality (n = 16 for each test condition). * = p ≤ 0.05, ** = p ≤ 0.01, *** = p ≤ 0.001.
Figure 5

Drug efficacy concentration range response curves for the top 16 rescue drugs. * = p ≤ 0.05, ** = p ≤ 0.01, and *** = p ≤ 0.001. n = 16 for each test condition.
Acknowledgments
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