A Salmonella nanoparticle mimic overcomes multidrug resistance in tumours

Nat Commun. 2016 Jul 25;7:12225. doi: 10.1038/ncomms12225.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • Animals
  • Bacterial Proteins / metabolism
  • Caspase 3 / metabolism
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Down-Regulation
  • Doxorubicin / pharmacology
  • Doxorubicin / therapeutic use
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Gold / chemistry
  • Humans
  • Metal Nanoparticles / chemistry*
  • Microfilament Proteins / metabolism
  • Models, Biological
  • Salmonella typhimurium / metabolism*


  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • Bacterial Proteins
  • Microfilament Proteins
  • SipA protein, Salmonella
  • Gold
  • Doxorubicin
  • Caspase 3