The obligate intracellular pathogen Chlamydia trachomatis targets host lipid droplets.
Lipid droplets (LDs) are ubiquitous but poorly understood neutral-lipid-rich eukaryotic organelles that may participate in functions as diverse as lipid homeostasis, membrane traffic, and signaling . We report that infection with the obligate intracellular pathogen Chlamydia trachomatis, the causative agent of trachoma and many sexually transmitted diseases , leads to the accumulation of neutral-lipid-rich structures with features of LDs at the cytoplasmic surface of the bacteria-containing vacuole. To identify bacterial factors that target these organelles, we screened a collection of yeast strains expressing GFP-tagged chlamydial ORFs and identified several proteins with tropism for eukaryotic LDs. We determined that three of these LD-associated (Lda) proteins are translocated into the mammalian host and associate with neutral-lipid-rich structures. Furthermore, the stability of one Lda protein is dependent on binding to LDs, and pharmacological inhibition of LD formation negatively impacted chlamydial replication. These results suggest that C. trachomatis targets LDs to enhance its survival and replication in infected cells. The co-option of mammalian LD function by a pathogenic bacterium represents a novel mechanism of eukaryotic organelle subversion and provides unique research opportunities to explore the function of these understudied organelles.
Kumar
Yadunanda
Y
Department of Molecular Genetics and Microbiology and Center for Microbial Pathogenesis, Duke University Medical Center, Durham, NC 27710, USA.
Cocchiaro
Jordan
J
Valdivia
Raphael H
RH
D001426:Bacterial Proteins / Q000378:metabolism*; D002692:Chlamydia trachomatis / Q000378:metabolism* / Q000472:pathogenicity; D049452:Green Fluorescent Proteins; D006367:HeLa Cells; D006801:Humans; D008055:Lipids; D008856:Microscopy, Fluorescence; D016366:Open Reading Frames / Q000235:genetics; D014617:Vacuoles / Q000378:metabolism*; D015003:Yeasts
D001426:Bacterial Proteins; D008055:Lipids; D049452:Green Fluorescent Proteins