In-vitro Antibacterial Activity and Mechanism of Monarda Didyma Essential Oils Against Carbapenem-resistant Klebsiella Pneumoniae

Overview

Journal BMC Microbiol

Publisher Biomed Central

Specialty Microbiology

Date 2023 Sep 20

PMID 37730531

Authors

Ying Chen

Jinda Zhao

Chenyu Liu

Dongmei Wu

Xianhe Wang

Affiliations

Soon will be listed here.

Abstract

To fight the global epidemic of drug-resistant bacteria, essential oils have gained increasing attention as a new source of antibiotics. The antimicrobial activity of Monarda didyma essential oils (MDEO) for the Carbapenem-resistant Klebsiella pneumoniae (CRKP) strains were determined by agar disc diffusion assay and broth microdilution assay. To further understand MDEO efficacy, a time-growth curve was performed. The biofilm formation of CRKP were determined by crystalline violet staining method, additionally, changes in intracellular Adenosine triphosphate (ATP), protein, Alkaline phosphatase (AKP) activities, and membrane integrity were investigated to assess the influence of MDEO on cell membrane damage. Finally, the activities of key enzymes in the tricarboxylic acid (TCA) pathways and pentose phosphate (PPP) pathways were examined to determine the effect of MDEO on the respiratory metabolism of CRKP. This study presents the antibacterial mechanism of MDEO against CRKP with a minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of 1.25 mg/ml. To understand MDEO efficacy, a time-kill kinetics approach was performed. The bactericidal effect of MDEO was evident at 2 h compared to the control at its MIC and 2MIC. Surface electron microscopic and ATP assay studies provided evidence for the multi-target action of MDEO against CRKP. MDEO could inhibit CRKP biofilm formation. MDEO could also cause irreversible damage to the CRKP cell membrane, resulting in the leakage of biological macromolecules (protein, ATP) and the reduction of intracellular enzymes (AKP) activities. Finally, MDEO affected the pathways of respiratory metabolism, such as PPP and TCA pathways. MDEO could reduce the activity of key enzymes (Glucose-6-phosphate dehydrogenase, citrate synthase, isocitrate dehydrogenase, and α-ketoglutarate dehydrogenase) in the PPP and TCA pathways to exert its biological effects against CRKP. These results suggest MDEO can exert inhibitory effects on CRKP, and potential mechanisms of action including inhibition of biofilm formation, damage of cell membrane structure and inhibition of energy metabolism.

Citing Articles

Thymol and carvacrol against : anti-bacterial, anti-biofilm, and synergistic activities-a systematic review.

Farhadi K, Rajabi E, Varpaei H, Iranzadasl M, Khodaparast S, Salehi M Front Pharmacol. 2024; 15:1487083.

PMID: 39512827 PMC: 11540684. DOI: 10.3389/fphar.2024.1487083.

References

Nazzaro F, Fratianni F, De Martino L, Coppola R, De Feo V . Effect of essential oils on pathogenic bacteria. Pharmaceuticals (Basel). 2013; 6(12):1451-74. PMC: 3873673. DOI: 10.3390/ph6121451. View

Di Vito M, Smolka A, Proto M, Barbanti L, Gelmini F, Napoli E . Is the Antimicrobial Activity of Hydrolates Lower than That of Essential Oils?. Antibiotics (Basel). 2021; 10(1). PMC: 7831920. DOI: 10.3390/antibiotics10010088. View

Kim H, Lee S, Byun Y, Park H . 6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Sci Rep. 2015; 5:8656. PMC: 4345325. DOI: 10.1038/srep08656. View

Higgins D, Chang R, Debabov D, Leung J, Wu T, Krause K . Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2005; 49(3):1127-34. PMC: 549257. DOI: 10.1128/AAC.49.3.1127-1134.2005. View

Qian W, Zhang J, Wang W, Wang T, Liu M, Yang M . Antimicrobial and antibiofilm activities of paeoniflorin against carbapenem-resistant Klebsiella pneumoniae. J Appl Microbiol. 2019; 128(2):401-413. DOI: 10.1111/jam.14480. View

Tamma P, Goodman K, Harris A, Tekle T, Roberts A, Taiwo A . Comparing the Outcomes of Patients With Carbapenemase-Producing and Non-Carbapenemase-Producing Carbapenem-Resistant Enterobacteriaceae Bacteremia. Clin Infect Dis. 2016; 64(3):257-264. PMC: 5241781. DOI: 10.1093/cid/ciw741. View

Junge W, Nelson N . ATP synthase. Annu Rev Biochem. 2015; 84:631-57. DOI: 10.1146/annurev-biochem-060614-034124. View

Wu S, Yang K, Hong Y, Gong Y, Ni J, Yang N . A New Perspective on the Antimicrobial Mechanism of Berberine Hydrochloride Against Revealed by Untargeted Metabolomic Studies. Front Microbiol. 2022; 13:917414. PMC: 9328669. DOI: 10.3389/fmicb.2022.917414. View

Marchese A, Orhan I, Daglia M, Barbieri R, Di Lorenzo A, Nabavi S . Antibacterial and antifungal activities of thymol: A brief review of the literature. Food Chem. 2016; 210:402-14. DOI: 10.1016/j.foodchem.2016.04.111. View

10.

Guo Y, Qu Y, Li W, Shen H, Cui J, Liu J . Protective effect of essential oil and its main component thymol on learning and memory impairment in aging mice. Front Pharmacol. 2022; 13:992269. PMC: 9464920. DOI: 10.3389/fphar.2022.992269. View

11.

Zhao Y, Chen M, Zhao Z, Yu S . The antibiotic activity and mechanisms of sugarcane (Saccharum officinarum L.) bagasse extract against food-borne pathogens. Food Chem. 2015; 185:112-8. DOI: 10.1016/j.foodchem.2015.03.120. View

12.

Ghaffari T, Kafil H, Asnaashari S, Farajnia S, Delazar A, Baek S . Chemical Composition and Antimicrobial Activity of Essential Oils from the Aerial Parts of Grown in Northwestern Iran. Molecules. 2019; 24(17). PMC: 6749391. DOI: 10.3390/molecules24173203. View

13.

Qian W, Wang W, Zhang J, Wang T, Liu M, Yang M . Antimicrobial and antibiofilm activities of ursolic acid against carbapenem-resistant Klebsiella pneumoniae. J Antibiot (Tokyo). 2020; 73(6):382-391. DOI: 10.1038/s41429-020-0285-6. View

14.

David S, Reuter S, Harris S, Glasner C, Feltwell T, Argimon S . Epidemic of carbapenem-resistant Klebsiella pneumoniae in Europe is driven by nosocomial spread. Nat Microbiol. 2019; 4(11):1919-1929. PMC: 7244338. DOI: 10.1038/s41564-019-0492-8. View

15.

Ben-David D, Kordevani R, Keller N, Tal I, Marzel A, Gal-Mor O . Outcome of carbapenem resistant Klebsiella pneumoniae bloodstream infections. Clin Microbiol Infect. 2011; 18(1):54-60. DOI: 10.1111/j.1469-0691.2011.03478.x. View

16.

Shirley M . Ceftazidime-Avibactam: A Review in the Treatment of Serious Gram-Negative Bacterial Infections. Drugs. 2018; 78(6):675-692. DOI: 10.1007/s40265-018-0902-x. View

17.

Qian W, Sun Z, Wang T, Yang M, Liu M, Zhang J . Antimicrobial activity of eugenol against carbapenem-resistant Klebsiella pneumoniae and its effect on biofilms. Microb Pathog. 2019; 139:103924. DOI: 10.1016/j.micpath.2019.103924. View

18.

Hoiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O . Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents. 2010; 35(4):322-32. DOI: 10.1016/j.ijantimicag.2009.12.011. View

19.

Di Domenico E, Rimoldi S, Cavallo I, DAgosto G, Trento E, Cagnoni G . Microbial biofilm correlates with an increased antibiotic tolerance and poor therapeutic outcome in infective endocarditis. BMC Microbiol. 2019; 19(1):228. PMC: 6802308. DOI: 10.1186/s12866-019-1596-2. View

20.

Sacks D, Baxter B, Campbell B, Carpenter J, Cognard C, Dippel D . Multisociety Consensus Quality Improvement Revised Consensus Statement for Endovascular Therapy of Acute Ischemic Stroke. Int J Stroke. 2018; 13(6):612-632. DOI: 10.1177/1747493018778713. View