title: Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection.
abstract: 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.
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Mirrashidi
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Cherilyn A
authors.initials: CA
authors.lastname: Elwell
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Erik
authors.initials: E
authors.lastname: Verschueren
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Johnson
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Frando
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: John
authors.initials: J
authors.lastname: Von Dollen
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Oren
authors.initials: O
authors.lastname: Rosenberg
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Natali
authors.initials: N
authors.lastname: Gulbahce
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Jang
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Tasha
authors.initials: T
authors.lastname: Johnson
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Jäger
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Anusha M
authors.initials: AM
authors.lastname: Gopalakrishnan
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Sherry
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Joe Dan
authors.initials: JD
authors.lastname: Dunn
authors.affiliation: Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Olive
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Bennett
authors.initials: B
authors.lastname: Penn
authors.affiliation: Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Shales
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jeffery S
authors.initials: JS
authors.lastname: Cox
authors.affiliation: Department of Microbiology, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Starnbach
authors.affiliation: Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, CT 06510, USA.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Derre
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University, Durham, NC 27710, USA.
authors.forename: Raphael
authors.initials: R
authors.lastname: Valdivia
authors.affiliation: QB3, California Institute for Quantitative Biosciences, San Francisco, CA 94148, USA; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94158, USA; Gladstone Institutes, San Francisco, CA 94158, USA. Electronic address: nevan.krogan@ucsf.edu.
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
authors.affiliation: Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: jengel@medicine.ucsf.edu.
authors.forename: Joanne
authors.initials: J
authors.lastname: Engel
mesh_terms: D001426:Bacterial Proteins / Q000032:analysis / Q000302:isolation & purification; D002690:Chlamydia Infections / Q000473:pathology; D002692:Chlamydia trachomatis / Q000276:immunology* / Q000378:metabolism* / Q000472:pathogenicity; D054884:Host-Pathogen Interactions; D006801:Humans; D002479:Inclusion Bodies / Q000737:chemistry* / Q000382:microbiology; D007425:Intracellular Membranes / Q000737:chemistry*; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome / Q000032:analysis*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome