TitleThe broad-spectrum antiviral compound ST-669 restricts chlamydial inclusion development and bacterial growth and localizes to host cell lipid droplets within treated cells.
Publication TypeJournal Article
Year of Publication2014
AuthorsSandoz, KM, Valiant, WG, Eriksen, SG, Hruby, DE, Allen, RD, Rockey, DD
JournalAntimicrob Agents Chemother
Date Published2014 Jul
KeywordsAnimals, Antiviral Agents, Cells, Cultured, Chlamydia, Chlamydia Infections, Coxiella burnetii, Genome, Bacterial, Humans, Inclusion Bodies, Lipids, Mice, Thiourea

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.

Alternate JournalAntimicrob Agents Chemother
PubMed ID24777097
PubMed Central IDPMC4068599
Grant ListR21 AI088540 / AI / NIAID NIH HHS / United States
RC1 AI086469 / AI / NIAID NIH HHS / United States
AI086469-01 / AI / NIAID NIH HHS / United States
AI088540-02 / AI / NIAID NIH HHS / United States