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Observation of efflux pump inhibition activity of naringenin, quercetin, and umbelliferone on
some multidrug-resistant microorganisms
Eda Altınöz*1, Ergin Murat Altuner1
1Department of Biology, Faculty of Science and Arts, Kastamonu University, Turkey
* altinozedaa@gmail.com
Abstract
Microorganisms affect every aspect of our lives. Especially pathogenic
and resistant microorganisms are microorganisms that prevent us
from living a healthy life. As a result of the unnecessary use of
antibiotics, bacterial resistance has emerged. One of the bacterial
resistance mechanisms is efflux pumps. In this in vitro study, it was
aimed to observe the inhibition of the efflux pumps by testing 3
compounds on a total of 8 strains, including Klebsiella pneumoniae,
Providencia rustigianii, Shigella flexneri, 4 clinically
isolated Escherichia coli, and E. coli ATCC 25922 having active efflux
pumps. The plant derived compounds used were naringenin,
quercetin and umbelliferone. Cartwheel method was applied by using
MIC/2 concentrations of the compounds. At the end of the test, UV
light was used to observe the efflux pump inhibition activities of
phytochemicals. According to the results of the study; the efflux
pump inhibition activity was observed only for naringenin. A further
study is recommended to determine the interaction mechanisms of
naringenin with specific efflux pump families.
Introduction Results
Conclusion
References
Naringenin
Quercetin
Graphical Abstract
Infectious diseases have been going on for many years and can result
in death [1]. Antibiotics have been used to cure infectious diseases.
The drugs used have gained resistance to microorganisms over time
and have reduced or destroyed the effectiveness of the drug. Efflux
pumps are one of these resistance mechanisms and are very
important.
Efflux pumps are known as important transport proteins that allow
toxic substances to be thrown from inside the cell to the outside of
the cell. These pumps are also found in all cells, prokaryotic and
eukaryotic [2]. The 5 most defined classes of efflux pump families
are: Master Facilitator (MF), Multi-Drug and Toxic Compound
Extrusion (MATE), Resistance-Nodulation-Fission (RND), Small Multi-
Drug Resistance (SMR), and ATP Binding Cassette (ABC) [3].
The chemical structures of naringenin and quercetin, which were
tested as inhibitors in the study, are given below.
[1] Drexler M. What You Need to Know about Infectious Disease. Institute of Medicine (US): National
Academies Press (US) (2010).
[2] Webber MA, Piddock LJV. The importance of efflux pumps in bacterial antibiotic resistance. Journal of
Antimicrobial Chemotherapy (2003) 51(1):9–11.
[3] Fernando D, Kumar A. Resistance-Nodulation-Division Multidrug Efflux Pumps in Gram-Negative Bacteria:
Role in Virulence. Antibiotics (2013) 2(1):163–181.
[4] National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 932, 5,7-
Dihydroxy-2-(4-hydroxyphenyl)chroman-4-one. https://pubchem.ncbi.nlm.nih.gov/compound/Naringenin.
[5] National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 5280343,
Quercetin. https://pubchem.ncbi.nlm.nih.gov/compound/Quercetin.
Naringenin 2D Structure [4]
Quercetin 2D Structure [5]
The efflux pump inhibition activity was observed only for naringenin
(Because EtBr remained in the cell, bound to the cell structure and radiated).
If non-toxic inhibitors are discovered, drug interaction can be increased by
inhibiting the resistance mechanism with clinical use.
