Selective Inhibitor of Endosomal Trafficking Pathways Exploited By
Selective inhibitor of endosomal trafficking pathways exploited by multiple toxins and viruses Eugene J. Gillespiea, Chi-Lee C. Hoa, Kavitha Balajib, Daniel L. Clemensc, Gang Dengd, Yao E. Wanga, Heidi J. Elsaessera, Batcha Tamilselvame,AmandeepGargie, Shandee D. Dixona,BryanFrancea,f, Brian T. Chamberlaind,f,StevenR.Blankee, Genhong Chenga, Juan Carlos de la Torreg, David G. Brooksa, Michael E. Jungd,f, John Colicellib, Robert Damoiseauxf, and Kenneth A. Bradleya,f,1 aDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095; bDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; cDepartment of Medicine, Division of Infectious Diseases, David Geffen School of Medicine, University of California, Los Angeles, CA 90095; dDepartment of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; eDepartment of Microbiology, Institute for Genomic Biology, University of Illinois at Urbana–Champaign, Champaign, IL 61801; fCalifornia NanoSystems Institute, University of California, Los Angeles, CA 90095; and gDepartment of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037 Edited by R. John Collier, Harvard Medical School, Boston, MA, and approved October 7, 2013 (received for review February 5, 2013) Pathogenic microorganisms and toxins have evolved a variety of by host proteases into 63- and 20-kDa fragments, allowing olig- mechanisms to gain access to the host-cell cytosol and thereby omerization of the toxin into a prepore (13). The PA oligomer exert virulent effects upon the host. One common mechanism of can then bind up to four monomers of LF, forming a holotoxin cellular entry requires trafficking to an acidified endosome, which complex (14, 15).
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