TY - JOUR
T1 - Global mapping of the inc-human interactome reveals that retromer restricts chlamydia infection
AU - Mirrashidi, Kathleen M.
AU - Elwell, Cherilyn A.
AU - Verschueren, Erik
AU - Johnson, Jeffrey R.
AU - Frando, Andrew
AU - Von Dollen, John
AU - Rosenberg, Oren
AU - Gulbahce, Natali
AU - Jang, Gwendolyn
AU - Johnson, Tasha
AU - Jager, Stefanie
AU - Gopalakrishnan, Anusha M.
AU - Sherry, Jessica
AU - Dan Dunn, Joe
AU - Olive, Andrew
AU - Penn, Bennett
AU - Shales, Michael
AU - Cox, Jeffery S.
AU - Starnbach, Michael N.
AU - Derre, Isabelle
AU - Valdivia, Raphael
AU - Krogan, Nevan J.
AU - Engel, Joanne
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015
Y1 - 2015
N2 - Chlamydia trachomatis is a leading cause of genital and ocular infections for which no vaccine exists. Upon entry into host cells, C. trachomatis resides within a membrane-bound compartmentâ€"the inclusionâ€" and secretes inclusion membrane proteins (Incs) that are thought to modulate the host-bacterium interface. To expand our understanding of Inc function(s), we subjected putative C. trachomatis Incs to affinity purification-mass spectroscopy (APMS). We identified Inc-human interactions for 38/58 Incs with enrichment in host processes consistent with Chlamydia’s intracellular life cycle. There is significant overlap between Inc targets and viral proteins, suggesting common pathogenic mechanisms among obligate intracellular microbes. IncE binds to sorting nexins (SNXs) 5/6, components of the retromer, which relocalizes SNX5/6 to the inclusion membrane and augments inclusion membrane tubulation. Depletion of retromer components enhances progeny production, revealing that retromer restricts Chlamydia infection. This study demonstrates the value of proteomics in unveiling hostpathogen interactions in genetically challenging microbes.
AB - Chlamydia trachomatis is a leading cause of genital and ocular infections for which no vaccine exists. Upon entry into host cells, C. trachomatis resides within a membrane-bound compartmentâ€"the inclusionâ€" and secretes inclusion membrane proteins (Incs) that are thought to modulate the host-bacterium interface. To expand our understanding of Inc function(s), we subjected putative C. trachomatis Incs to affinity purification-mass spectroscopy (APMS). We identified Inc-human interactions for 38/58 Incs with enrichment in host processes consistent with Chlamydia’s intracellular life cycle. There is significant overlap between Inc targets and viral proteins, suggesting common pathogenic mechanisms among obligate intracellular microbes. IncE binds to sorting nexins (SNXs) 5/6, components of the retromer, which relocalizes SNX5/6 to the inclusion membrane and augments inclusion membrane tubulation. Depletion of retromer components enhances progeny production, revealing that retromer restricts Chlamydia infection. This study demonstrates the value of proteomics in unveiling hostpathogen interactions in genetically challenging microbes.
UR - http://www.scopus.com/inward/record.url?scp=84943186180&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2015.06.004
DO - 10.1016/j.chom.2015.06.004
M3 - Article
C2 - 26118995
AN - SCOPUS:84943186180
SN - 1931-3128
VL - 18
SP - 109
EP - 121
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 1
ER -