Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Pentacyclic Triterpenoids as Antibiofilm Agents against Methicillinresistant and Biofilm-forming Staphylococcus aureus (MRSA)

Author(s): Pooi Yin Katrina Chung*, Ming Yi Gan and Beek Yoke Chin

Volume 23, Issue 6, 2022

Published on: 09 August, 2021

Page: [828 - 834] Pages: 7

DOI: 10.2174/1389201022666210806092643

Price: $65

Abstract

Background: Methicillin-resistant Staphylococcus aureus (MRSA) has been constantly evolv-ing and developing resistance against conventional antibiotics. One of the key features of MRSA that enables it to develop resistance to antibiotics and host immune system is its ability to form biofilm in indwelling medical devices. In previous studies, the antimicrobial activity and mechanisms of action of three known pentacyclic triterpenoids α-amyrin, betulinic acid and betulinaldehyde against planktonic cells of MRSA were determined and elucidated.

Objective: This study was carried out to evaluate the ability of the three compounds to significantly reduce the biomass of pre-formed biofilms of MRSA and metabolic activity of the bacterial cells in the biofilm.

Methods: The anti-biofilm activity of α-amyrin, betulinic acid and betulinaldehyde, individually and in combination with oxacillin or vancomycin, against reference strain of MRSA in pre-formed biofilm were evaluated using the crystal violet and resazurin assays.

Results: α-amyrin and betulinic acid significantly reduced the biomass of pre-formed biofilms of MRSA as individual compounds and in combination with oxacillin or vancomycin. Although betulinaldehyde individually increased the biomass, selected combinations with oxacillin and vancomycin were able to reduce the biomass. All three compounds did not show cytotoxic properties on normal mammalian cells.

Conclusion: The three pentacyclic triterpenoids could significantly reduce pre-formed biofilm of MRSA with no cytotoxic effects on normal mammalian cells. These findings demonstrated that pentacyclic triterpenoids have the potential to be developed further as antibiofilm agents against MRSA cells in bio-films, to combat infections caused by multidrug-resistant and biofilm-forming S. aureus.

Keywords: Biofilm, pentacyclic triterpenoids, methicillin-resistant, Staphylococcus aureus, antibiotics, biomass.

« Previous Next »
Graphical Abstract

[1]
Woo, S.G.; Lee, S.M.; Lee, S.Y.; Lim, K.H.; Ha, E.J.; Kim, S.H.; Eom, Y.B. The effectiveness of anti-biofilm and anti-virulence properties of dihydrocelastrol and dihydrocelastryl diacetate in fighting against methicillin-resistant Staphylococcus aureus. Arch. Microbiol., 2017, 199(8), 1151-1163.
[http://dx.doi.org/10.1007/s00203-017-1386-x] [PMID: 28487997]
[2]
Wojnicz, D.; Tichaczek-Goska, D.; Kicia, M. Pentacyclic triterpenes combined with ciprofloxacin help to eradicate the biofilm formed in vitro by Escherichia coli. Indian J. Med. Res., 2015, 141(3), 343-353.
[http://dx.doi.org/10.4103/0971-5916.156631] [PMID: 25963496]
[3]
Chung, P.Y.; Navaratnam, P.; Chung, L.Y. Synergistic antimicrobial activity between pentacyclic triterpenoids and antibiotics against Staphylococcus aureus strains. Ann. Clin. Microbiol. Antimicrob., 2011, 10, 25.
[http://dx.doi.org/10.1186/1476-0711-10-25] [PMID: 21658242]
[4]
Chung, P.Y.; Chung, L.Y.; Navaratnam, P. Potential targets by pentacyclic triterpenoids from Callicarpa farinosa against methicillin-resistant and sensitive Staphylococcus aureus. Fitoterapia, 2014, 94, 48-54.
[http://dx.doi.org/10.1016/j.fitote.2014.01.026] [PMID: 24508863]
[5]
Antunes, A.L.S.; Trentin, D.S.; Bonfanti, J.W.; Pinto, C.C.; Perez, L.R.; Macedo, A.J.; Barth, A.L. Application of a feasible method for determination of biofilm antimicrobial susceptibility in staphylococci. APMIS, 2010, 118(11), 873-877.
[http://dx.doi.org/10.1111/j.1600-0463.2010.02681.x] [PMID: 20955460]
[6]
Nair, S.; Desai, S.; Poonacha, N.; Vipra, A.; Sharma, U. Antibiofilm activity and synergistic inhibition of Staphylococcus aureus biofilms by bactericidal protein P128 in combination with antibiotics. Antimicrob. Agents Chemother., 2016, 60(12), 7280-7289.
[PMID: 27671070]
[7]
Tacconelli, E.; Carrara, E.; Savoldi, A.; Harbarth, S.; Mendelson, M.; Monnet, D.L.; Pulcini, C.; Kahlmeter, G.; Kluytmans, J.; Carmeli, Y.; Ouellette, M.; Outterson, K.; Patel, J.; Cavaleri, M.; Cox, E.M.; Houchens, C.R.; Grayson, M.L.; Hansen, P.; Singh, N.; Theuretzbacher, U.; Magrini, N. WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect. Dis., 2018, 18(3), 318-327.
[http://dx.doi.org/10.1016/S1473-3099(17)30753-3] [PMID: 29276051]
[8]
James, G.A.; Swogger, E.; Wolcott, R. Pulcini, Ed.; Secor, P.; Sestrich, J.; Costerton, J.W.; Stewart, P.S. Biofilms in chronic wounds. Wound Repair Regen., 2008, 16(1), 37-44.
[http://dx.doi.org/10.1111/j.1524-475X.2007.00321.x] [PMID: 18086294]
[9]
Stoodley, P.; Sauer, K.; Davies, D.G.; Costerton, J.W. Biofilms as complex differentiated communities. Annu. Rev. Microbiol., 2002, 56, 187-209.
[http://dx.doi.org/10.1146/annurev.micro.56.012302.160705] [PMID: 12142477]
[10]
Sandberg, M.; Määttänen, A.; Peltonen, J.; Vuorela, P.M.; Fallarero, A. Automating a 96-well microtitre plate model for Staphylococcus aureus biofilms: an approach to screening of natural antimicrobial compounds. Int. J. Antimicrob. Agents, 2008, 32(3), 233-240.
[http://dx.doi.org/10.1016/j.ijantimicag.2008.04.022] [PMID: 18640013]
[11]
Sandberg, M.E.; Schellmann, D.; Brunhofer, G.; Erker, T.; Busygin, I.; Leino, R.; Vuorela, P.M.; Fallarero, A. Pros and cons of using resazurin staining for quantification of viable Staphylococcus aureus biofilms in a screening assay. J. Microbiol. Methods, 2009, 78(1), 104-106.
[http://dx.doi.org/10.1016/j.mimet.2009.04.014] [PMID: 19427338]
[12]
Mirani, Z.A.; Aziz, M.; Khan, M.N.; Lal, I.; Hassan, N.U.; Khan, S.I. Biofilm formation and dispersal of Staphylococcus aureus under the influence of oxacillin. Microb. Pathog., 2013, 61-62, 66-72.
[http://dx.doi.org/10.1016/j.micpath.2013.05.002] [PMID: 23711963]
[13]
He, X.; Yuan, F.; Lu, F.; Yin, Y.; Cao, J. Vancomycin-induced biofilm formation by methicillin-resistant Staphylococcus aureus is associated with the secretion of membrane vesicles. Microb. Pathog., 2017, 110, 225-231.
[http://dx.doi.org/10.1016/j.micpath.2017.07.004] [PMID: 28687320]
[14]
Liu, Q.; Yeo, W.S.; Bae, T. The SaeRS two-component system of Staphylococcus aureus. Genes (Basel), 2016, 7(10), 81.
[http://dx.doi.org/10.3390/genes7100081] [PMID: 27706107]
[15]
El-Alfy, T.S.; Ezzat, S.M.; Hegazy, A.K.; Amer, A.M.; Kamel, G.M. Isolation of biologically active constituents from Moringa peregrina (Forssk.) Fiori. (family: Moringaceae) growing in Egypt. Pharmacogn. Mag., 2011, 7(26), 109-115.
[http://dx.doi.org/10.4103/0973-1296.80667] [PMID: 21716619]
[16]
Quintal-Novelo, C.; Moo-Puc, R.E.; Chale-Dzul, J.; Cáceres-Farfán, M.; Mendez-Gonzalez, M.; Borges-Argáez, R. Cytotoxic constituents from the stem bark of Diospyros cuneata Standl. Nat. Prod. Res., 2013, 27(17), 1594-1597.
[http://dx.doi.org/10.1080/14786419.2012.738201] [PMID: 23098219]
[17]
Zuco, V.; Supino, R.; Righetti, S.C.; Cleris, L.; Marchesi, E.; Gambacorti-Passerini, C.; Formelli, F. Selective cytotoxicity of betulinic acid on tumor cell lines, but not on normal cells. Cancer Lett., 2002, 175(1), 17-25.
[http://dx.doi.org/10.1016/S0304-3835(01)00718-2] [PMID: 11734332]

Rights & Permissions Print Cite
Article Metrics
23
1
© 2024 Bentham Science Publishers | Privacy Policy