Record Details

The Broad-Spectrum Antiviral Compound ST-669 Restricts Chlamydial Inclusion Development and Bacterial Growth and Localizes to Host Cell Lipid Droplets within Treated Cells

ScholarsArchive at Oregon State University

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Title The Broad-Spectrum Antiviral Compound ST-669 Restricts Chlamydial Inclusion Development and Bacterial Growth and Localizes to Host Cell Lipid Droplets within Treated Cells
Names Sandoz, Kelsi M. (creator)
Valiant, William G. (creator)
Eriksen, Steven G. (creator)
Hruby, Dennis E. (creator)
Allen, Robert D., III (creator)
Rockey, Daniel D. (creator)
Date Issued 2014-04-28 (iso8601)
Note This is the publisher’s final pdf. The published article is copyrighted by the American Society for Microbiology and can be found at: http://aac.asm.org/.
Abstract Novel broad-spectrum antimicrobials are a critical component of a strategy for combating antibiotic-resistant pathogens. In this
study, we explored the activity of the broad-spectrum antiviral compound ST-669 for activity against different intracellular bacteria
and began a characterization of its mechanism of antimicrobial action. ST-669 inhibits the growth of three different species
of chlamydia and the intracellular bacterium Coxiella burnetii in Vero and HeLa cells but not in McCoy (murine) cells. The antichlamydial
and anti-C. burnetii activity spectrum was consistent with those observed for tested viruses, suggesting a common
mechanism of action. Cycloheximide treatment in the presence of ST-669 abrogated the inhibitory effect, demonstrating that
eukaryotic protein synthesis is required for tested activity. Immunofluorescence microscopy demonstrated that different chlamydiae
grow atypically in the presence of ST-669, in a manner that suggests the compound affects inclusion formation and organization.
Microscopic analysis of cells treated with a fluorescent derivative of ST-669 demonstrated that the compound localized
to host cell lipid droplets but not to other organelles or the host cytosol. These results demonstrate that ST-669 affects intracellular
growth in a host-cell-dependent manner and interrupts proper development of chlamydial inclusions, possibly through a
lipid droplet-dependent process.
Genre Article
Identifier Sandoz, K. M., Valiant, W. G., Eriksen, S. G., Hruby, D. E., Allen, R. D., & Rockey, D. D. (2014). The broad spectrum antiviral compound ST-669 restricts Chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells. Antimicrobial Agents and Chemotherapy, 58(7), 3860-3866. doi:10.1128/AAC.02064-13

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