Inhibition of the multidrug efflux pump LmrS from Staphylococcus aureus by cumin spice Cuminum cyminum.
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.
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Prathusha
P
Kakarla
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Jared
J
Floyd
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
MunMun
M
Mukherjee
Department of Biological Sciences, College of Arts and Sciences, University of North Texas, 1155 Union Circle #305220, Denton, TX, 76203, USA.
Amith R
AR
Devireddy
Department of Biological Sciences, College of Arts and Sciences, University of North Texas, 1155 Union Circle #305220, Denton, TX, 76203, USA.
Madhuri A
MA
Inupakutika
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Indrika
I
Ranweera
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Ranjana
R
Kc
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Ugina
U
'Shrestha
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Upender Rao
UR
Cheeti
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Thomas Mark
TM
Willmon
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Jaclyn
J
Adams
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA.
Merissa
M
Bruns
Bioinformatics Division, Osmania University, Hyderabad, Telangana, 500007, India.
Shravan Kumar
SK
Gunda
Department of Biology, Eastern New Mexico University, Portales, NM, 88130, USA. Manuel.Varela@enmu.edu.
Manuel F
MF
Varela
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D028527:Cuminum / Q000737:chemistry*; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects* / Q000235:genetics; D004996:Ethidium / Q000378:metabolism; D019450:Genes, MDR / Q000235:genetics / Q000502:physiology*; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000037:antagonists & inhibitors; D010936:Plant Extracts / Q000494:pharmacology*; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004996:Ethidium; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010936:Plant Extracts
Cumin; Dietary spice; Efflux; Efflux pump inhibitor; LmrS; MRSA; Multidrug resistance; Natural antimicrobials; Spices; Staphylococcus aureus