title: Chlamydia trachomatis Infection Leads to Defined Alterations to the Lipid Droplet Proteome in Epithelial Cells.
abstract: The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and a main cause of genital and ocular diseases. During its intracellular cycle, C. trachomatis replicates inside a membrane-bound vacuole termed an "inclusion". Acquisition of lipids (and other nutrients) from the host cell is a critical step in chlamydial replication. Lipid droplets (LD) are ubiquitous, ER-derived neutral lipid-rich storage organelles surrounded by a phospholipids monolayer and associated proteins. Previous studies have shown that LDs accumulate at the periphery of, and eventually translocate into, the chlamydial inclusion. These observations point out to Chlamydia-mediated manipulation of LDs in infected cells, which may impact the function and thereby the protein composition of these organelles. By means of a label-free quantitative mass spectrometry approach we found that the LD proteome is modified in the context of C. trachomatis infection. We determined that LDs isolated from C. trachomatis-infected cells were enriched in proteins related to lipid metabolism, biosynthesis and LD-specific functions. Interestingly, consistent with the observation that LDs intimately associate with the inclusion, a subset of inclusion membrane proteins co-purified with LD protein extracts. Finally, genetic ablation of LDs negatively affected generation of C. trachomatis infectious progeny, consistent with a role for LD biogenesis in optimal chlamydial growth.
authors.affiliation: Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Hector Alex
authors.initials: HA
authors.lastname: Saka
authors.affiliation: Proteomics and Metabolomics Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: J Will
authors.initials: JW
authors.lastname: Thompson
authors.affiliation: Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Yi-Shan
authors.initials: YS
authors.lastname: Chen
authors.affiliation: Proteomics and Metabolomics Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Laura G
authors.initials: LG
authors.lastname: Dubois
authors.affiliation: Department of Biochemistry and Biophysics, UCSF, San Francisco, California, United States of America.
authors.forename: Joel T
authors.initials: JT
authors.lastname: Haas
authors.affiliation: Proteomics and Metabolomics Core Facility, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Arthur
authors.initials: A
authors.lastname: Moseley
authors.affiliation: Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, North Carolina, United States of America.
authors.forename: Raphael H
authors.initials: RH
authors.lastname: Valdivia
mesh_terms: D000818:Animals; D002460:Cell Line; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D002692:Chlamydia trachomatis; D004847:Epithelial Cells / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D050356:Lipid Metabolism; D051379:Mice; D020543:Proteome; D040901:Proteomics / Q000379:methods
chemical_list: D020543:Proteome