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.
Highlights
The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and the causative agent of genital and ocular diseases
In order to assess if any changes were induced in the Lipid droplets (LD) proteome upon infection with C. trachomatis, LDs were isolated from uninfected cells and from cells infected with C. trachomatis LGV-L2 for 20 hours or 40 hours
We performed an ultrastructural analysis by transmission electron microscopy (TEM) of LDs in uninfected and C. trachomatis-infected cells fixed in the presence of malachite green to preserve lipid structures [41]
Summary
The obligate intracellular bacterium Chlamydia trachomatis is a major human pathogen and the causative agent of genital and ocular diseases. In the United States, direct medical costs of genital infections caused by C. trachomatis have reached costs as high as half a billion dollars annually [4] This bacterium is the etiologic agent of trachoma, an ocular disease endemic in 56 countries and the main cause of infectious blindness. LDs accumulated at the periphery of the inclusion and the neutral lipid content increased in epithelial cells infected with. LDs can be translocated into the lumen of the chlamydial inclusion, the significance of these phenomena is unclear [30] These observations lead us to predict that Chlamydia alters the function of LDs in infected cells, a process that should be reflected by defined changes in the protein composition of these organelles. We found a subset of inclusion membrane proteins co-purifying with LDs, consistent with the notion that C. trachomatis inclusion intimately associates with LDs
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