Autophagy Induction by a Small Molecule Inhibits Salmonella Survival in Macrophages and Mice.

Autophagy Induction by a Small Molecule Inhibits Salmonella Survival in Macrophages and Mice. Antimicrob Agents Chemother. 2019 Oct 07;: Authors: Nagy TA, Quintana JLJ, Reens AL, Crooks AL, Detweiler CS Abstract Salmonella enterica are natural bacterial pathogens of humans and animals that cause systemic infection or gastroenteritis. During systemic infection, Salmonella generally reside within professional phagocytes, typically macrophages, whereas gastroenteritis is caused by infection of epithelial cells. We are only beginning to understand which host pathways contribute to Salmonella survival in particular cell types. We therefore sought to identify compounds that perturb Salmonella-host interactions using a chemical genetics approach. We found one small molecule, D61, that reduces Salmonella load in cell-line and primary macrophages but has no effect on Salmonella growth in epithelial cells or rich medium. We determined that in macrophages D61 induces LC3II, a marker of the autophagy pathway, and promotes aggregation of LC3II near Salmonella We found that D61 antibacterial activity depends on the VPS34 complex and on ATG5. D61 also reduced Salmonella load in the spleens and livers of infected mice. Lastly, we demonstrate that D61 antibacterial activity in macrophages is synergistic with the antibiotic chloramphenicol, but that this synergy is largely independent of the known autophagy-stimulating activity of chloramphenicol. Thu...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research