Details

Autor(en) / Beteiligte

• Mirrashidi, Kathleen M.
• Elwell, Cherilyn A.
• Verschueren, Erik
• Johnson, Jeffrey R.
• Frando, Andrew
• Von Dollen, John
• Rosenberg, Oren
• Gulbahce, Natali
• Jang, Gwendolyn
• Johnson, Tasha
• Jäger, Stefanie
• Gopalakrishnan, Anusha M.
• Sherry, Jessica
• Dunn, Joe Dan
• Olive, Andrew
• Penn, Bennett
• Shales, Michael
• Cox, Jeffery S.
• Starnbach, Michael N.
• Derre, Isabelle
• Valdivia, Raphael
• Krogan, Nevan J.
• Engel, Joanne

Titel

Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection

Ist Teil von

• Cell host & microbe, 2015-07, Vol.18 (1), p.109-121

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2015

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 compartment—the inclusion—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 (AP-MS). 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 host-pathogen interactions in genetically challenging microbes. [Display omitted] •Chlamydia inclusion membrane (Inc)-human protein interactions were identified by AP-MS•Bacterial and viral pathogens share human protein targets•IncE directly binds the PX domains of retromer components SNX5 and SNX6•Retromer restricts Chlamydia infection and promotes inclusion tubulation Chlamydia inclusion membrane proteins are uniquely positioned at the host-pathogen interface, but their host targets are largely unknown. Mirrashidi et al. report a Chlamydia-human protein-protein interactome that identifies host proteins and pathways implicated in pathogenesis. They show that Chlamydia sequesters retromer components to potentially overcome host mechanisms of pathogen restriction.