Survival curves of wild-type and perforin-2 (mpeg1) deficient mice challenged with Yersinia pseudotuberculosis or an isogenic cif::aadA mutant

<b>Figure 8</b>. Survival of C57Bl/6 mice inoculated orogastrically with 10^8 CFU of <i>Yersinia pseudotuberculosis</i> or an isogenic <i>cif::aadA</i> mutant. <br><b>Figure 9</b>. Survival curves for two different lineages of perforin-2 (Mpeg1) +/+, +/−, and −/− mice after orogastric inoculation with 10^6 CFU of <i>Yersinia pseudotuberculosis</i> or an isogenic <i>cif::aadA</i> mutant.<br>The accompanying <b>Dataset/Table</b> contains the data for Figures 8 and 9. This data was originally published in "<i>Enteric Pathogens Deploy Cell Cycle Inhibiting Factors to Block the Bactericidal Activity of Perforin-2</i>," McCormack, Lyapichev,Olsson, Podack, and Munson. Elife. 2015 Sep 29;4:e06505. doi: 10.7554/eLife.06505.PMID: 26418746 PMCID: PMC4626573 DOI: 10.7554/eLife.06505. Published under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original authors and source are credited. <br>Please see the citation for methods and experimental details.<br><br>Abstract of associated publication: Perforin-2 (MPEG1) is an effector of the innate immune system that limits the proliferation and spread of medically relevant Gram-negative, -positive, and acid fast bacteria. We show here that a cullin-RING E3 ubiquitin ligase (CRL) complex containing cullin-1 and βTrCP monoubiquitylates Perforin-2 in response to pathogen associated molecular patterns such as LPS. Ubiquitylation triggers a rapid redistribution of Perforin-2 and is essential for its bactericidal activity. Enteric pathogens such as Yersinia pseudotuberculosis and enteropathogenic Escherichia coli disarm host cells by injecting cell cycle inhibiting factors (Cifs) into mammalian cells to deamidate the ubiquitin-like protein NEDD8. Because CRL activity is dependent upon NEDD8, Cif blocks ubiquitin dependent trafficking of Perforin-2 and thus, its bactericidal activity. Collectively, these studies further underscore the biological significance of Perforin-2 and elucidate critical molecular events that culminate in Perforin-2-dependent killing of both intracellular and extracellular, cell-adherent bacteria.