Trans-Cinnamaldehyde Inhibitory Activity Against <i>mrkA</i>, <i>treC</i>, and <i>luxS</i> Genes in Biofilm-forming <i>Klebsiella pneumoniae</i>: An In Silico Study
Keywords:pkCSM, Molecular Docking, Klebsiella pneumoniae, Trans-Cinnamaldehyde, Antimicrobial
Biofilm-forming Klebsiella pneumoniae is a multidrug resistant organism that causes severe infections in humans. The luxS, treC and mrkA genes play a significant role in the formation of K. pneumoniae biofilms. Cinnamaldehyde has been shown to exhibit antimicrobial and antibiofilm activities against pathogenic bacteria. The present study aims to investigate the antibiofilm activity of cinnamaldehyde in silico.
In silico study was done using Autodock Vina software and pharmacokinetics prediction using the pkCSM strategy. The ability of cinnamaldehyde to inhibit the mrkA, treC, and luxS genes of K. pneumonia was accessed by docking the 3D structure of cinnamaldehyde with the luxS, mrkA, and treC gene receptors. Post-docking analysis such as binding affinities, hydrophobic interactions, and pharmacokinetic predictions were carried out. Cinnamaldehyde showed low binding affinities for the three genes; luxS (-5.6 kcal/mol), mrkA (-5.0 kcal/mol), and treC (-6.0 kcal/mol). The root mean square deviation (RMSD) values were found to be 1.461, 1.210, and 1.426 for luxS, mrkA, and treC gene receptors, respectively. Cinnamaldehyde had a number of hydrophobic interactions as seen in the ligand-receptor interactions for luxS (Lys 13; Asn 15; His 11; Pro 43; Leu 159; and Val 9), mrkA (Phe 157; Ala 162; and Lys 129). Cinnamaldehyde had high bond-free energy similar to that of ciprofloxacin docked with the same gene receptor. From the pharmacokinetics predictions, cinnamaldehyde had a good pharmacokinetics profile. In conclusion, cinnamaldehyde has a high docking score comparable to ciprofloxacin and therefore has a potential for use as antibacterial and antibiofilm agent against Klebsiella pneumoniae.
Effah CY, Sun T, Liu S, Wu Y. Klebsiella pneumoniae: An increasing threat to public health. Ann Clin Microbiol Antimicrob. 2020; 19:1–9.
Paczosa MK and Mecsas J. Klebsiella pneumoniae: Going on the Offense with a Strong Defense. Microbiol Mol Biol Rev. 2016; 80:629–661.
Karimi K, Zarei O, Sedighi P, Taheri M, Doosti-Irani A, Shokoohizadeh L . Investigation of Antibiotic Resistance and Biofilm Formation in Clinical Isolates of Klebsiella pneumoniae. Int J Microbiol. 2021; 2021:5573388.
Shadkam S, Goli HR, Mirzaei B, Gholami M and Ahanjan M. Correlation between antimicrobial resistance and biofilm formation capability among Klebsiella pneumoniae strains isolated from hospitalized patients in Iran. Ann Clin Microbiol Antimicrob. 2021; 20:1–7.
De Oliveira Júnior NG and Franco OL. Promising strategies for future treatment of Klebsiella pneumoniae biofilms. Fut Microbiol. 2020; 15:63–79.
Wang Z, Ding Z, Li Z, Ding Y, Jiang F, Liu J. Antioxidant and antibacterial study of 10 flavonoids revealed rutin as a potential antibiofilm agent in Klebsiella pneumoniae strains isolated from hospitalized patients. Microb Pathog. 2021; 159:105121.
Chen L, Chen L, Wilksch JJ, Liu H, Zhang X, Torres VL, Bi W, Cao EMJ, Li J, Lithgow T, Zhou T. Investigation of Lux S-mediated quorum sensing in Klebsiella pneumoniae. J Med Microbiol. 2020; 69:402–413.
Balestrino D, Haagensen JAJ, Rich C, Forestier C. Characterization of type 2 quorum sensing in Klebsiella pneumoniae and relationship with biofilm formation. J. Bacteriol. 2005; 187(8):2870–2880.
Hammad AA, Mohammed JA, Abdulrazzaq SA, Jasim SA. Evaluate The Relation Between Luxs Gene and The Biofilm Production By Klebsiella pneumoniae. PalArch’s J Archaeol Egypt/Egyptol. 2020; 17:7632–7639.
Wu MC, Lin T-L, Hsieh P-F, Yang H-C, Wang J-T. Isolation of genes involved in biofilm formation of a Klebsiella pneumoniae strain causing pyogenic liver abscess. PLoS One 2011; 6(8):e23500.
Johnson JG. Regulation of Type 3 Fimbrial Gene Expression in Klebsiella pneumoniae. PhD Dissertation, University of Iowa, Summer 2011. 1–156 p.
Guerra MES, Destro G, Vieira B, Lima AS, Ferraz LFC, Hakansson AP, Darrieux M, Convers TR. Klebsiella pneumoniae Biofilms and Their Role in Disease Pathogenesis. Front Cell Infect Microbiol. 2022; 12:1–13.
Brown DG, Lister T, May-Dracka TL. New natural products as new leads for antibacterial drug discovery. Bioorganic Med Chem Lett. 2014; 24:413–418.
Bjarnsholt T, Ciofu O, Molin S, Givskov M, Høiby N. Applying insights from biofilm biology to drug development-can a new approach be developed? Nat Rev Drug Discov. 2013; 12:791–808.
Blackledge MS, Worthington RJ, Melander C. Biologically inspired strategies for combating bacterial biofilms. Curr Opin Pharmacol. 2013; 13:699–706.
Lebeaux D, Ghigo J-M, Beloin C. Biofilm-Related Infections: Bridging the Gap between Clinical Management and Fundamental Aspects of Recalcitrance toward Antibiotics. Microbiol Mol Biol Rev. 2014; 78:510–543.
Wu H, Moser C, Wang HZ, Høiby N, Song ZJ. Strategies for combating bacterial biofilm infections. Int J Oral Sci. 2015; 7:1–7.
Taraszkiewicz A, Fila G, Grinholc M, Nakonieczna J. Innovative Strategies to OvercomeBiofilm Resistance. Biomed Res Int. 2013; 2013:150653.
Martin C. Wan L, Abhishek G, Mohd CIMA, Iza R, Stephen BT, Prem R, Ken K(MA). Strategies for 19.Antimicrobial Drug Delivery to Biofilm. Curr Pharm Des. 2015; 21(1):43–66.
Moloney MG. Natural Products as a Source for Novel Antibiotics. Trends Pharmacol Sci. 2016; 37:689–701.
Yap PSX, Yiap BC, Ping HC, Lim SHE. Essential Oils, A New Horizon in Combating Bacterial Antibiotic Resistance. Open Microbiol J. 2014; 8:6–14.
Tariq S, Wani S, Rasool W, Shafi K, Bhat MA, Prabhakar A, Shalla AH, Rather MA. A comprehensive review of the antibacterial, antifungal and antiviral potential of essential oils and their chemical constituents against drug-resistant microbial pathogens. Microb Pathog. 2019; 134:103580.
Yang S-K, Yusoff K, Ajat M, Thomas W, Abushelaibi A, Akseer R, Lim S-HE, Lai K-S. Disruption of KPC-producing Klebsiella pneumoniae membrane via induction of oxidative stress by cinnamon bark (Cinnamomum verum J. Presl) essential oil. PLoS One 2019; 14:1–20.
Vasconcelos NG, Croda J, Simionatto S. Antibacterial mechanisms of cinnamon and its constituents: A review. Microb Pathog. 2018; 120:198–203.
Rao PV and Gan SH. Cinnamon: A multifaceted medicinal plant. Evid-Based Compl Altern Med. 2014; 2014:642942.
Novita S. The Effect of Cinnamomum burmannii Water Extraction Against Staphylococcus aureus, Enterobacter spp., Pseudomonas aeruginosa, and Candida albicans: In Vitro Study. Folia Medica Indones. 2019; 55:285–289.
Kim Y, Kim S, Cho KH, Lee JH, Lee J. Antibiofilm Activities of Cinnamaldehyde Analogs against Uropathogenic Escherichia coli and Staphylococcus aureus. Int J Mol Sci. 2022; 23(13):7225.
Gembloux D and Biophysique C. The hydrophobic. Rev Lit Arts Am. 2020; 535–540.
Patil M, Choudhari AS, Pandita S, Islam A, Raina P, Kaul-Ghanekar R. Cinnamaldehyde, Cinnamic Acid, and Cinnamyl Alcohol, the Bioactives of Cinnamomum cassia Exhibit HDAC8 Inhibitory Activity: An In vitro and In silico Study. Pharmacogn Mag. 2017; 13:S645-S651.
Casini R, Degl’Innocenti EL, E., Landolfi M, Bueno JT. On the Atomic Polarization of the Ground Level of Na I. The Astrophys J. 2002; 573:864–871.
da Nóbrega Alves D, Monteiro AFM, Andrade PN, Lazarini JG, Abílio GMF, Guerra FQS, Scotti MT, Scotti L, Rosalen PL, Castro RD. Docking Prediction, Antifungal Activity, Anti-Biofilm Effects on Candida spp., and Toxicity against Human Cells of Cinnamaldehyde. Molecules. 2020; 25(24):5969.
El-Baz AM, Mosbah RA, Goda RM, Mansour B, Sultana T, Dahms TES, El-Ganiny AM. Back to Nature: Combating Candida albicans Biofilm, Phospholipase and Hemolysin Using Plant Essential Oils. Antibiotics (Basel). 2021;10(1):81.
Wahyuningsih D, Purnomo Y, Tilaqza A. In Silico Study of Pulutan (Urena lobata) Leaf Extract as Anti Inflammation and their ADME Prediction. J Trop Pharm Chem. 2022; 6:30–37.
Yeni Y and Rachmania RA. The Prediction of Pharmacokinetic Properties of Compounds in Hemigraphis alternata (Burm.F.) T. Ander Leaves Using pkCSM. Indones J Chem. 2022; 22:1081–1089.
How to Cite
Copyright (c) 2023 Tropical Journal of Natural Product Research (TJNPR)
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.