A broad-spectrum antibiotic, DCAP, reduces uropathogenic Escherichia coli infection and enhances vorinostat anticancer activity by modulating autophagy

Cell Death & Disease
Giulia AllavenaBenedetto Grimaldi

Abstract

The cellular recycling pathway of autophagy plays a fundamental role in adaptive responses to nutrient deprivation and other forms of stress under physiological and pathological conditions. However, autophagy can also be a double-edge sword during certain bacterial infections (such as urinary tract infections) and in cancer, where it can be hijacked by the pathogens and cancer cells, respectively, to promote their own survival. Thus, autophagy modulation can potentially have multiple effects in multiple contexts and this property can be leveraged to improve outcomes. In this report, we identify that a broad-spectrum antibiotic, 2-((3-(3, 6-dichloro-9H-carbazol-9-yl)-2-hydroxypropyl) amino)-2-(hydroxymethyl) propane-1, 3-diol (DCAP) modulates autophagy. We employed combined biochemical, fluorescence microscopy and correlative light electron microscopy approaches to demonstrate that DCAP treatment blocks autophagy at the late stages by preventing autophagolysosome maturation and interrupting the autophagic flux. We further show that, DCAP significantly reduces UPEC infection in urinary tract epithelial cells via inhibition of autophagy. Finally, we reveal that DCAP enhances the anticancer activity of the histone acetyltransferase...Continue Reading

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Citations

Jan 4, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Arduino A MangoniDiego Muñoz-Torrero

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Methods Mentioned

BETA
fluorescence microscopy
Light Electron Microscopy
electron microscopy
scraping
Immunoprecipitation
Assay
Fluorescence Imaging

Software Mentioned

GraphPad Prism
Compusyn
ImageQuant
ImageJ

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