Inhibition of the multidrug efflux pump LmrS from Staphylococcus aureus by cumin spice Cuminum cyminum

Arch Microbiol. 2017 Apr;199(3):465-474. doi: 10.1007/s00203-016-1314-5. Epub 2016 Nov 9.

Abstract

Staphylococcus aureus is a serious causative agent of infectious disease. Multidrug-resistant strains like methicillin-resistant S. aureus compromise treatment efficacy, causing significant morbidity and mortality. Active efflux represents a major antimicrobial resistance mechanism. The proton-driven multidrug efflux pump, LmrS, actively exports structurally distinct antimicrobials. To circumvent resistance and restore clinical efficacy of antibiotics, efflux pump inhibitors are necessary, and natural edible spices like cumin are potential candidates. The mode of cumin antibacterial action and underlying mechanisms behind drug resistance inhibition, however, are unclear. We tested the hypothesis that cumin inhibits LmrS drug transport. We found that cumin inhibited bacterial growth and LmrS ethidium transport in a dosage-dependent manner. We demonstrate that cumin is antibacterial toward a multidrug-resistant host and that resistance modulation involves multidrug efflux inhibition.

Keywords: Cumin; Dietary spice; Efflux; Efflux pump inhibitor; LmrS; MRSA; Multidrug resistance; Natural antimicrobials; Spices; Staphylococcus aureus.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Cuminum / chemistry*
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Ethidium / metabolism
  • Genes, MDR / genetics
  • Genes, MDR / physiology*
  • Methicillin-Resistant Staphylococcus aureus / drug effects*
  • Microbial Sensitivity Tests
  • Multidrug Resistance-Associated Proteins / antagonists & inhibitors
  • Plant Extracts / pharmacology*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Multidrug Resistance-Associated Proteins
  • Plant Extracts
  • Ethidium