International network for natural sciences – research journal
  • mendeley icon
  • linkedin icon
  • google plus icon
  • twitter icon
  • google scholar icon
  • facebook icon

Elucidating the Differences in the Biofilm Suppression Mechanism of 6-Gingerol and 6-Shogaol in Pseudomonas aeruginosa through Molecular Docking

By: John Sylvester B. Nas, Francisco R. Gellecanao, Danica M. Malacad, Jose Alfonso G. Manugas, Gildred Christian L. Mutia, Mikaela D. Paguibitan, Mark Johndel M. Quilala, Trisha Joy Basille A. Rodriguez, Mary Janniezl S. Tee

Key Words: 6-shogaol, 6-gingerol, Pseudomonas aeruginosa, biofilm, molecular docking.

Int. J. Biosci. 18(2), 1-10, February 2021.


Certification: ijb 2021 0149 [Generate Certificate]


The virulence of Pseudomonas aeruginosa (P. aeruginosa) is associated with its biofilm formation via quorum sensing. Compounds present in Zingiber officinale (Z. officinale) such as 6-gingerol and 6-shogaol show antibacterial property against different bacteria. However, the mechanism of action of these compounds is underexplored. Hence, we compared the biofilm reduction of these compounds and visualized their binding interactions to different pathways to hypothesize a possible mechanism of action associated with the biofilm reduction. In this study, the biofilm formation of P. aeruginosa treated with varying concentrations of either 6-shogaol or 6-gingerol was determined through biofilm accumulation assay. The binding affinity of 6-gingerol and 6-shogaol with various enzymes involved in the membrane integrity, lipopolysaccharide formation, motility, and fatty acid synthesis were ranked through molecular docking. The crystal structures of the compounds docked to the top 3 enzymes with the most negative docking score were evaluated. Results show that 6-gingerol suppressed the biofilm formation of P. aeruginosa significantly higher (p<0.05) than 6-shogaol. Besides, 6-gingerol has a strong binding affinity to an enzyme associated with membrane integrity while 6-shogaol to a motility-related enzyme. The top enzymes were associated with membrane integrity, lipopolysaccharide formation, and motility. The differences in the binding affinity of 6-gingerol and 6-shogaol may be attributed to the varying substructures involved during the non-covalent interactions. Moreover, we speculate that there are other factors involved that resulted in a higher binding affinity of 6-shogaol despite having fewer interactions. These factors may be independent or complementary with the non-covalent bonding, which may be essential to their biofilm suppression property.

| Views 231 |

| Views 231 |

Elucidating the Differences in the Biofilm Suppression Mechanism of 6-Gingerol and 6-Shogaol in Pseudomonas aeruginosa through Molecular Docking

Al Bayssari C, Dabboussi F, Hamze M, Rolain JM. 2015. Emergence of carbapenemase-producing Pseudomonas aeruginosa and Acinetobacter baumannii in livestock animals in Lebanon. Journal of Antimicrobial Chemotherapy 70(3), 950-951.

Bodey GP, Bolivar R, Fainstein V, Jadeja L. 1983. Infections caused by Pseudomonas aeruginosa. Reviews of infectious diseases 5(2), 279-313.

Chen D, Oezguen N, Urvil P, Ferguson C, Dann SM, Savidge TC. 2016. Regulation of protein-ligand binding affinity by hydrogen bond pairing. Science advances 2(3), e1501240.

Dubois-Brissonnet F, Trotier E, Briandet R. 2016. The biofilm lifestyle involves an increase in bacterial membrane saturated fatty acids. Frontiers in microbiology 7, p 1673.

Ha SK, Moon E, Ju MS, Kim DH, Ryu JH, Oh MS, Kim SY. 2012. 6-Shogaol, a ginger product, modulates neuroinflammation: a new approach to neuroprotection. Neuropharmacology 63(2), 211-223.

Ham SY, Kim HS, Cha E, Park JH, Park HD. 2018. Mitigation of membrane biofouling by a quorum quenching bacterium for membrane bioreactors. Bioresource technology 258, 220-226.

Ham SY, Kim HS, Jang Y, Sun PF, Park JH, Lee JS, Byun Y, Park HD. 2019. Control of membrane biofouling by 6-gingerol analogs: Quorum sensing inhibition. Fuel 250, 79-87.

Kim HS, Park HD. 2013. Ginger extract inhibits biofilm formation by Pseudomonas aeruginosa PA14. PloS one 8(9), e76106.

Kim HS, Lee SH, Byun Y, Park HD. 2015. 6-Gingerol reduces Pseudomonas aeruginosa biofilm formation and virulence via quorum sensing inhibition. Scientific reports 5, 8656.

Korni FMM, Khalil F. 2017. Effect of ginger and its nanoparticles on growth performance, cognition capability, immunity and prevention of motile Aeromonas septicaemia in Cyprinus carpio fingerlings. Aquaculture Nutrition 23(6), 1492-1499.

Kostakioti M, Hadjifrangiskou M, Hultgren SJ. 2013. Bacterial biofilms: development, dispersal, and therapeutic strategies in the dawn of the postantibiotic era. Cold Spring Harbor perspectives in medicine 3(4), a010306.

Kufareva I, Abagyan R. 2011. Methods of protein

structure comparison. In Homology Modeling 857, 231-257.

Lee JH, Kim YG, Choi P, Ham J, Park JG, Lee J. 2018. Antibiofilm and antivirulence activities of 6-gingerol and 6-shogaol against Candida albicans due to hyphal inhibition. Frontiers in Cellular and Infection Microbiology 8, 299.

Li Y, Hao G, Galvani CD, Meng Y, Fuente LDL, Hoch HC, Burr TJ. 2007. Type I and type IV pili of Xylella fastidiosa affect twitching motility, biofilm formation and cell–cell aggregation. Microbiology  153(3), 719-726.

Mobley DL, Gilson MK. 2017. Predicting binding free energies: frontiers and benchmarks. Annual review of biophysics 46, 531-558.

Myslinski JM, Clements JH, DeLorbe JE, Martin SF. 2013. Protein–Ligand Interactions: Thermodynamic Effects Associated with Increasing the Length of an Alkyl Chain. ACS medicinal chemistry letters 4(11), 1048-1053.

Nakao R, Ramstedt M, Wai SN, Uhlin BE. 2012. Enhanced biofilm formation by Escherichia coli LPS mutants defective in Hep biosynthesis. PloS one 7(12),  e51241.

Nas JSB, Roxas CKF, Acero RRG, Gamit ALP, Kim JP, Rentutar JA, Ching AC, Saludares AQ. 2019. Solanum melongena (Eggplant) Crude Anthocyanin Extract and Delphinidin-3-glucoside protects Caenorhabditis elegans against Staphylococcus aureus and Klebsiella pneumoniae. Philippine Journal of Health Research and Development 23(4), 17-24.

Nikolić M, Vasić S, Đurđević J, Stefanović O, Čomić L. 2014. Antibacterial and anti-biofilm activity of ginger (Zingiber officinale (Roscoe)) ethanolic extract. Kragujevac Journal of Science (36), 129-136.

O’Toole GA, Kolter R. 1998. Flagellar and twitching motility are necessary for Pseudomonas aeruginosa biofilm development. Molecular microbiology 30(2), 295-304.

Saha P, Das B, Chaudhuri K. 2013. Role of 6-gingerol in reduction of cholera toxin activity in vitro and in vivo. Antimicrobial agents and chemotherapy 57(9), 4373-4380.

Sasidharan I, Menon AN. 2010. Comparative chemical composition and antimicrobial activity fresh & dry ginger oils (Zingiber officinale Roscoe). International Journal of Current Pharmaceutical Research 2(4), 40-43.

Schroth MN, Cho JJ, Green SK, Kominos SD. 2018. Epidemiology of Pseudomonas aeruginosa in agricultural areas. J. Med. Microbiol 67, 1191-1201.

Sela S, Hammer-Muntz O, Krifucks O, Pinto R, Weisblit L, Leitner G. 2007. Phenotypic and genotypic characterization of Pseudomonas aeruginosa strains isolated from mastitis outbreaks in dairy herds. The Journal of Dairy Research 74(4), 425.

Shi X, Rao NN, Kornberg A. 2004. Inorganic polyphosphate in Bacillus cereus: motility, biofilm formation, and sporulation. Proceedings of the National Academy of Sciences 101(49), 17061-17065.

Smith AJ, Zhang X, Leach AG, Houk KN. 2009. Beyond picomolar affinities: quantitative aspects of noncovalent and covalent binding of drugs to proteins. Journal of medicinal chemistry 52(2), 225-233.

Suekawa M, Ishige A, Yuasa K, Sudo K, Aburada M, Hosoya E. 1984. Pharmacological studies on ginger. I. Pharmacological actions of pungent constituents, (6)-gingerol and (6)-shogaol. Journal of pharmacobio-dynamics 7(11), 836-848.

Weng CJ, Wu CF, Huang HW, Ho CT, Yen GC. 2010. Anti‐invasion effects of 6‐shogaol and 6‐gingerol, two active components in ginger, on human hepatocarcinoma cells. Molecular nutrition & food research 54(11), 1618-1627.

Wilson C, Lukowicz R, Merchant S, Valquier-Flynn H, Caballero J, Sandoval J, Okuom M, Huber C, Brooks TD, Wilson E, Clement B. 2017. Quantitative and qualitative assessment methods for biofilm growth: A mini-review. Research & reviews. Journal of engineering and technology 6(4).

Wolfe AJ, Millikan DS, Campbell JM, Visick KL. 2004. Vibrio fischeri σ54 controls motility, biofilm formation, luminescence, and colonization. Applied and Environmental Microbiology 70(4), 2520-2524.

John Sylvester B. Nas, Francisco R. Gellecanao, Danica M. Malacad, Jose Alfonso G. Manugas, Gildred Christian L. Mutia, Mikaela D. Paguibitan, Mark Johndel M. Quilala, Trisha Joy Basille A. Rodriguez, Mary Janniezl S. Tee.
Elucidating the Differences in the Biofilm Suppression Mechanism of 6-Gingerol and 6-Shogaol in Pseudomonas aeruginosa through Molecular Docking.
Int. J. Biosci. 18(2), 1-10, February 2021.
Copyright © 2021
By Authors and International Network for
Natural Sciences (INNSPUB)
innspub logo
english language editing
    Publish Your Article
    Submit Your Article
Email Update