Host-directed antimicrobial drugs with broad-spectrum efficacy against intracellular bacterial pathogens.
Bottom Line: Combining host- and pathogen-directed treatments is a strategy to decrease the emergence of drug-resistant intracellular bacterial pathogens.Importance: Although antibiotic treatment is often successful, it is becoming clear that alternatives to conventional pathogen-directed therapy must be developed in the face of increasing antibiotic resistance.Moreover, the costs and timing associated with the development of novel antimicrobials make repurposed FDA-approved drugs attractive host-targeted therapeutics.
Affiliation: Howard Taylor Ricketts Laboratory, University of Chicago, Argonne National Laboratory, Lemont, Illinois, USA Department of Microbiology, University of Chicago, Chicago, Illinois, USA.Show MeSH
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Mentions: To independently evaluate the role of cholesterol trafficking in the intracellular growth of C. burnetii, we constructed THP-1 cell lines with decreased levels of NPC-1, a transporter that facilitates the export of cholesterol from late endosomes and lysosomes. We found that reducing the expression of NPC-1 decreased the intracellular growth of C. burnetii (Fig. 4A and B). We infer that the intracellular movement of cholesterol is a key determinant of C. burnetii growth that can be interrupted by a wide variety of FDA-approved drugs.
Affiliation: Howard Taylor Ricketts Laboratory, University of Chicago, Argonne National Laboratory, Lemont, Illinois, USA Department of Microbiology, University of Chicago, Chicago, Illinois, USA.