Department of Microbiology and Physiological Systems; Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine
Cancer Biology | Microbiology | Nanotechnology | Translational Medical Research
Salmonella enterica serotype Typhimurium is a food-borne pathogen that also selectively grows in tumours and functionally decreases P-glycoprotein (P-gp), a multidrug resistance transporter. Here we report that the Salmonella type III secretion effector, SipA, is responsible for P-gp modulation through a pathway involving caspase-3. Mimicking the ability of Salmonella to reverse multidrug resistance, we constructed a gold nanoparticle system packaged with a SipA corona, and found this bacterial mimic not only accumulates in tumours but also reduces P-gp at a SipA dose significantly lower than free SipA. Moreover, the Salmonella nanoparticle mimic suppresses tumour growth with a concomitant reduction in P-gp when used with an existing chemotherapeutic drug (that is, doxorubicin). On the basis of our finding that the SipA Salmonella effector is fundamental for functionally decreasing P-gp, we engineered a nanoparticle mimic that both overcomes multidrug resistance in cancer cells and increases tumour sensitivity to conventional chemotherapeutics.
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DOI of Published Version
Nat Commun. 2016 Jul 25;7:12225. doi: 10.1038/ncomms12225. Link to article on publisher's site
Mercado-Lubo, Regino; Zhang, Yuanwei; Zhao, Liang; Rossi, Kyle; Wu, Xiang; Zou, Yekui; Castillo, Antonio; Leonard, Jack L.; Bortell, Rita; Greiner, Dale L.; Shultz, Leonard D.; Han, Gang; and McCormick, Beth A., "A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours" (2016). UMass Center for Clinical and Translational Science Supported Publications. 151.
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This work is licensed under a Creative Commons Attribution 4.0 License.