J Appl Biomed 20:15-21, 2022 | DOI: 10.32725/jab.2022.002
Evaluation of anti-methicillin-resistant Staphylococcus aureus property of zerumbone
- 1 University of Baghdad, College of Science, Department of Biology, Baghdad, Iraq
- 2 University of Karachi, International Center for Chemical and Biological Sciences, H.E.J. Research Institute of Chemistry, Karachi, Pakistan
- 3 Universiti Putra Malaysia, Faculty of Veterinary Medicine, Department of Veterinary Laboratory Diagnosis, Serdang, Selangor, Malaysia
- 4 Universiti Putra Malaysia, Faculty of Veterinary Medicine, Department of Veterinary Preclinical Sciences, Serdang, Selangor, Malaysia
Context and objective: Zerumbone has been reported to exert anti-microbial effects, but the mechanism by which the compound exerts its action is not known. Thus, this study aimed to investigate the mechanism of action of zerumbone against methicillin-resistance Staphylococcus aureus (MRSA), using the atomic force microscopy (AFM), scanning electron microscopy (SEM), and flow cytometry techniques.
Methods: MRSA (NCTC 13277) cell viability was determined using the microplate AlamarBlue assay. AFM and SEM were used to determine the morphology of zerumbone-treated MRSA cells. Flow cytometric analysis was used to determine the effect of zerumbone on bacterial membrane permeability and membrane potential, using the propidium iodide (PI) staining method, membrane potential-sensitive fluorescence probe, and DiBAC4(3) dye. DCFDA dye was used to determine the generation of reactive oxygen species (ROS) by MRSA.
Results: Zerumbone significantly inhibited MRSA growth with a minimum inhibitory concentration (MIC) of 125 µg/ml. The AFM analysis showed that zerumbone caused leakage of cytoplasmic content from the bacterial cells. Ultrastructure analysis showed small colonies of the bacteria with pores on the membrane surface. There were increases in zerumbone-treated MRSA PI and DiBAC4(3) fluorescence, indicating an increase in cell membrane permeability and a decrease in membrane potential that culminated in the loss of membrane structural integrity and bacterial death. Based on DCFDA dye analysis, zerumbone also reduced ROS production by MRSA.
Conclusions: Zerumbone exerts anti-MRSA effects by causing membrane depolarization, increasing membrane permeability, and finally disrupting cell membrane and bacterial killing.
Keywords: Atomic force microscopy; DiBAC4(3); Flow cytometry; Propidium iodide; Zerumbone
Conflicts of interest:
The authors have no conflict of interests to declare.
Received: March 13, 2020; Revised: December 6, 2021; Accepted: December 21, 2021; Prepublished online: February 11, 2022; Published: March 17, 2022 Show citation
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References
- Abdul AB, Abdelwahab SI, Al-Zubairi AS, Elhassan MM, Murali SM (2008). Anticancer and antimicrobial activities of zerumbone from the rhizomes of Zingiber zerumbut. Int J Pharmacol 4(4): 301-304. DOI: 10.3923/ijp.2008.301.304.
Go to original source...
- Al-Ani LKT, Yonus MI, Mahdii BA, Omer MA, Taher JK, Albaayit SFA, Al-Khoja SB (2018). First record of use Fusarium proliferatum fungi in direct treatment to control the adult of wheat flour Tribolium confusum, as well as, use the entomopathogenic fungi Beauveria. Ecol Environ Conserv 24 (3): 29-34.
- Albaayit SFA (2020). In vitro evaluation of anticancer activity of Moringa peregrina seeds on breast cancer cells. Eurasia Proc Sci Technol Eng Math 11: 163-166.
- Albaayit SFA (2021a). Evaluation of anti-methicillin resistant Staphylococcus aureus property of Clausena excavata leaves by usingatomic force microscopy and flowcytometry techniques. Pak J Agri Sci 58(1): 315-320. DOI: 10.21162/PAKJAS/21.921.
Go to original source...
- Albaayit SFA (2021b). Enzyme inhibitory properties of zerumbone. Pak J Agri Sci 58(3): 1207-1209. DOI: 10.21162/PAKJAS/21.9759.
Go to original source...
- Albaayit SFA, Maharjan R (2018). Immunomodulation of Zerumbone via Decreasing the Production of Reactive Oxygen Species from Immune Cells. Pak J Biol Sci 21(9): 475-479. DOI: 10.3923/pjbs.2018.475.479.
Go to original source...
Go to PubMed...
- Albaayit SFA, Ozaslan M (2019). Cytotoxic and Urease Inhibition Potential of Moringa peregrina Seed Ethanolic Extract. Int J Pharmacol 15(1): 151-155. DOI: 10.3923/ijp.2019.151.155.
Go to original source...
- Albaayit SFA, Abba Y, Abdullah R, Abdullah N (2014). Evaluation of antioxidant activity and acute toxicity of Clausena excavata leaves extract. Evid Based Complement Alternat Med 2014: 975450. DOI: 10.1155/2014/97545.
Go to original source...
- Albaayit SFA, Abba Y, Abdullah R, Abdullah N (2015). Effect of Clausena excavata Burm. F. (Rutaceae) leaf extract on wound healing and antioxidant activity in rats. Drug Des Devel Ther 9: 3507-3518. DOI: 10.2147/DDDT.S84770.
Go to original source...
Go to PubMed...
- Albaayit SFA, Abba Y, Abdullah R, Abdullah N (2016). Prophylactic effects of Clausena excavata Burum. f. leaf extract in ethanol-induced gastric ulcers. Drug Des Devel Ther 10: 1973-1986. DOI: 10.2147/DDDT.S103993.
Go to original source...
Go to PubMed...
- Albaayit SFA, Abdullah R, Abdullah N (2020a). Zerumbone-loaded nanostructured lipid carrier gel facilitates wound healing in rats. Rev Bras Farmacogn 30(2): 272-278. DOI: 10.1007/s43450-020-00023-7.
Go to original source...
- Albaayit SFA, Al-Khafaji ASK, Alnaimy HS (2019). In vitro macrophage nitric oxide and interleukin-1 beta suppression by Moringa peregrina seed. Turk J Pharm Sci 16(3): 362-365. DOI: 10.4274/tips.galenos.2018.52244.
Go to original source...
- Albaayit SFA, Khan MA, Abdullah R (2021c). Zerumbone induces growth inhibition of Burkitt's lymphoma cell line via apoptosis. Nat Volatiles Essent Oils 8(3): 56-63. DOI: 10.37929/nveo.927770.
Go to original source...
- Albaayit SFA, Khan MA, Abdullah R, Noor MHM (2021d). Ethyl acetate extract of Clausena excavata induces growth inhibition of non-small-lung cancer, NCI-H460, cell line via apoptosis. J Appl Biomed 19(1): 40-47. DOI: 10.32725/jab.2021.007.
Go to original source...
Go to PubMed...
- Albaayit SFA, Maharjan R, Abdullah R, Noor MHM (2021b). Anti-Enterococcus faecalis, Cytotoxicity, Phytotoxicity, and Anticancer Studies on Clausena excavata Burum. f. (Rutaceae) Leaves. Biomed Res Int 2021: 3123476. DOI: 10.1155/2021/3123476.
Go to original source...
Go to PubMed...
- Albaayit SFA, Maharjan R, Khan M (2021a). Evaluation of hemolysis activity of Zerumbone on RBCs and brine shrimp toxicity. Baghdad Sci J 18(1): 65-69. DOI:10.21123/bsj.2021.18.1.0065.
Go to original source...
- Albaayit SFA, Rasedee A, Abdullah N, Abba Y (2020b). Methanolic extract of Clausena excavata promotes wound healing via antiinflammatory and anti-apoptotic activities. Asian Pac J Trop Biomed 10(5): 232-238. DOI: 10.4103/2221-1691.281467.
Go to original source...
- Al-Bahrani RM, Radif HM, Albaayit SFA (2020). Evaluation of potent silver nanoparticles production from Agaricus bisporus against Helicobacter pylori. Pak J Agri Sci 57(4): 1197-1201. DOI: 10.21162/PAKJAS/20.9893.
Go to original source...
- Al-Naddawi THS, Albaayit SFA, Khalaf ZZ (2019). The Synergism and Antagonism behavior of Aqueous Extraction for Black Tea, Green Tea and Coffee against the Effectiveness of Certain Antibiotics. Eurasia Proc Sci Technol Eng Math 6: 39-42.
- Ashraf SM, Sebastian J, Rathinasamy K (2019). Zerumbone, a cyclic sesquiterpene, exerts antimitotic activity in HeLa cells through tubulin binding and exhibits synergistic activity with vinblastine and paclitaxel. Cell Prolif 52(2): e12558. DOI: 10.1111/cpr.12558.
Go to original source...
Go to PubMed...
- Belley A, McKay GA, Arhin FF, Sarmiento I, Beaulieu S, Fadhil I, et al. (2010). Oritavancin disrupts membrane integrity of Staphylococcus aureus and vancomycin-resistant enterococci to effect rapid bacterial killing. Antimicrob Agents Chemother 54(12): 5369-5371. DOI: 10.1128/AAC.00760-10.
Go to original source...
Go to PubMed...
- Benbelaïd F, Khadir A, Abdoune MA, Bendahou M, Muselli A, Costa J (2014). Antimicrobial activity of some essential oils against oral multidrug-resistant Enterococcus faecalis in both planktonic and biofilm state. Asian Pac J Trop Biomed 4(6): 463-472. DOI: 10.12980/APJTB.4.2014C1203.
Go to original source...
Go to PubMed...
- Bui T, Straus DS (1998). Effects of cyclopentenone prostaglandins and related compounds on insulin-like growth factor-I and Waf1 gene expression. Biochim Biophys Acta 1397(1): 31-42. DOI: 10.1016/S0167-4781(97)00214-5.
Go to original source...
Go to PubMed...
- Clementi EA, Marks LR, Roche-Håkansson H, Håkansson AP (2014). Monitoring changes in membrane polarity, membrane integrity, and intracellular ion concentrations in Streptococcus pneumoniae using fluorescent dyes. J Vis Exp 84: e51008. DOI: 10.3791/51008.
Go to original source...
Go to PubMed...
- da Silva TM, Pinheiro CD, Orlandi PP, Pinheiro CC, Pontes GS (2018). Zerumbone from Zingiber zerumbet (L.) smith: a potential prophylactic and therapeutic agent against the cariogenic bacterium Streptococcus mutans. BMC Complement Altern Med 18(1): 301. DOI: 10.1186/s12906-018-2360-0.
Go to original source...
Go to PubMed...
- Dhama K, Tiwari R, Chakraborty S, Saminathan M, Kumar A, Karthik K, et al. (2014). Evidence based antibacterial potentials of medicinal plants and herbs countering bacterial pathogens especially in the era of emerging drug resistance: An integrated update. Int J Pharmacol 10(1): 1-43. DOI: 10.3923/ijp.2014.1.43.
Go to original source...
- Fang Z, Xu L, Lin Y, Cai X, Wang S (2019). The preservative potential of Octopus scraps peptides-Zinc chelate against Staphylococcus aureus: Its fabrication, antibacterial activity and action mode. Food control 98: 24-33. DOI: 10.1016/j.foodcont.2018.11.015.
Go to original source...
- Farooq S, Wahab AT, Fozing CD, Rahman AU, Choudhary MI (2014). Artonin I inhibits multidrug resistance in Staphylococcus aureus and potentiates the action of inactive antibiotics in vitro. J Appl Microbiol 117(4): 996-1011. DOI: 10.1111/jam.12595.
Go to original source...
Go to PubMed...
- Fischer ER, Hansen BT, Nair V, Hoyt FH, Dorward DW (2012). Scanning Electron Microscopy. Curr Protoc Microbiol 25: 2B.2.1-2B.2.47. DOI: 10.1002/9780471729259.mc02b02s25.
Go to original source...
Go to PubMed...
- Girisa S, Shabnam B, Monisha J, Fan L, Halim CE, Arfuso F, et al. (2019). Potential of zerumbone as an anti-cancer agent. Molecules 24(4): 734. DOI: 10.3390/molecules24040734.
Go to original source...
Go to PubMed...
- Hwang S, Jo M, Hong JE, Park CO, Lee CG, Yun M, Rhee K-J (2019). Zerumbone Suppresses Enterotoxigenic Bacteroides fragilis Infection-Induced Colonic Inflammation through Inhibition of NF-κB. Int J Mol Sci 20(18): 4560. DOI: 10.3390/ijms20184560.
Go to original source...
Go to PubMed...
- Ibrahim MY, Abdul AB, Ibrahim TAT, Abdelwahab SI, Elhassan MM, Syam MM (2010). Evaluation of acute toxicity and the effect of single injected doses of zerumbone on the kidney and liver functions in Sprague Dawley rats. Afr J Biotechnol 9(28): 4442-4450.
- Ibraheem HT, Al-Mathkhury HJF (2018). pvl-carried methicillin resistant Staphylococcus aureus isolated from hospitalized patients in Baghdad, Iraq. Iraqi J Sci 59(4B): 1967-1972. DOI: 10.24996/ijs.2018.59.4B.1.
Go to original source...
- Imlay JA, Fridovich I (1991). Superoxide production by respiring membranes of Escherichia coli. Free Radic Res Commun 12-13 Pt 1: 59-66. DOI: 10.3109/10715769109145768.
Go to original source...
Go to PubMed...
- Jin YB, Seo WD, Lee YJ, Lee YS, Lee HJ (2013). Toxicological evaluation of zerumbone on antitumor effects in mice. Afr J Pharm Pharmacol 7(8): 466-473. DOI: 10.5897/AJPP2012.0001.
Go to original source...
- Kalantari K, Moniri M, Boroumand Moghaddam A, Abdul Rahim R, Bin Ariff A, Izadiyan Z, Mohamad R (2017). A review of the biomedical applications of zerumbone and the techniques for its extraction from ginger rhizomes. Molecules 22(10): 1645. DOI: 10.3390/molecules22101645.
Go to original source...
Go to PubMed...
- Kim HS, Lee JH, Kim IK (1996). Intracellular glutathione level modulates the induction of apoptosis by Δ12-prostaglandin J2. Prostaglandins 51(6): 413-425. DOI: 10.1016/0090-6980(96)00047-0.
Go to original source...
Go to PubMed...
- Kitayama T, Iwabuchi R, Minagawa S, Sawada S, Okumura R, Hoshino K, et al. (2007). Synthesis of a novel inhibitor against MRSA and VRE: preparation from zerumbone ring openingmaterial showing histidine-kinase inhibition. Bioorg Med Chem Lett 17(4): 1098-1101. DOI: 10.1016/j.bmcl.2006.11.015.
Go to original source...
Go to PubMed...
- Lancaster MV, Fields RD (1996). Antibiotic and cytotoxic drug susceptibility assays using resazurin and poising agents. U.S. Patent No. 5,501,959A. Washington DC: U.S. Patent and Trademark Office.
- McAuley S, Huynh A, Czarny TL, Brown ED, Nodwell JR (2018). Membrane activity profiling of small molecule B. subtilis growth inhibitors utilizing novel duel-dye fluorescence assay. MedChemComm 9(3): 554-561. DOI: 10.1039/c8md00009c.
Go to original source...
Go to PubMed...
- Mudzengi CP, Murwira A, Tivapasi M, Murungweni C, Burumu JV, Halimani T (2017). Antibacterial activity of aqueous and methanol extracts of selected species used in livestock health management. Pharm Biol 55(1): 1054-1060. DOI: 10.1080/13880209.2017.1287744.
Go to original source...
Go to PubMed...
- Murakami A, Takahashi D, Kinoshita T, Koshimizu K, Kim HW, Yoshihiro A, et al. (2002). Zerumbone, a Southeast Asian ginger sesquiterpene, markedly suppresses free radical generation, proinflammatory protein production, and cancer cell proliferation accompanied by apoptosis: the α,β-unsaturated carbonyl group is a prerequisite. Carcinogenesis 23(5): 795-802. DOI: 10.1093/carcin/23.5.795.
Go to original source...
Go to PubMed...
- Rodríguez AM, Enriz RD, Santagata LN, Jáuregui EA, Pestchanker MJ, Giordano OS (1997). Structure-cytoprotective activity relationship of simple molecules containing an α,β-unsaturated carbonyl system. J Med Chem 40(12): 1827-1834. DOI: 10.1021/jm960280m.
Go to original source...
Go to PubMed...
- Santosh Kumar SC, Srinivas P, Negi PS, Bettadaiah BK (2013). Antibacterial and antimutagenic activities of novel zerumbone analogues. Food Chem 141(2): 1097-1103. DOI: 10.1016/j.foodchem.2013.04.021.
Go to original source...
Go to PubMed...
- Siddique H, Pendry B, Rahman MM (2019). Terpenes from Zingiber montanum and Their Screening against Multi-Drug Resistant and Methicillin Resistant Staphylococcus aureus. Molecules 24(3): 385. DOI: 10.3390/molecules24030385.
Go to original source...
Go to PubMed...
- Sithara T, Dhanya BP, Arun KB, Sini S, Dan M, Kokkuvayil Vasu R, Nisha P (2018). Zerumbone, a cyclic sesquiterpene from Zingiber zerumbet induces apoptosis, cell cycle arrest, and antimigratory effects in SW480 colorectal cancer cells. J Agric Food Chem 66(3): 602-612. DOI: 10.1021/acs.jafc.7b04472.
Go to original source...
Go to PubMed...
- Tian M, Wu X, Hong Y, Wang H, Deng G, Zhou Y (2020). Comparison of chemical composition and bioactivities of essential oils from fresh and dry rhizomes of Zingiber zerumbet (L.) Smith. Biomed Res Int 2020: 9641284. DOI: 10.1155/2020/9641284.
Go to original source...
Go to PubMed...
- Tjalkens RB, Luckey SW, Kroll DJ, Petersen DR (1998). α,β-Unsaturated Aldehydes Increase GlutathioneS-Transferase mRNA and Protein: Correlation with Activation of the Antioxidant Response Element. Arch Biochem Biophys 359(1): 42-50. DOI: 10.1006/abbi.1998.0895.
Go to original source...
Go to PubMed...
- Vishwanatha HN, Niraguna Babu P, Gowrishankar BS, Shridhar SB (2012). Antimicrobial activity of zerumbone from Zingiber zurumbet against Staphylococcus epidermidis and Aspergillus spp. IJABPT 3(4): 40-43.
- Wu Y, Bai J, Zhong K, Huang Y, Qi H, Jiang Y, Gao H. (2016). Antibacterial activity and membrane-disruptive mechanism of 3-p-trans-coumaroyl-2-hydroxyquinic acid, a novel phenolic compound from pine needles of Cedrus deodara, against Staphylococcus aureus. Molecules 21(8): 1084. DOI: 10.3390/molecules21081084.
Go to original source...
Go to PubMed...
- Zhang S, Liu Q, Liu Y, Qiao H, Liu Y (2012). Zerumbone, a Southeast Asian ginger sesquiterpene, induced apoptosis of pancreatic carcinoma cells through p53 signaling pathway. Evid Based Complement Alternat Med 2012: 936030. DOI: 10.1155/2012/936030.
Go to original source...
Go to PubMed...
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