Login Register Cart 0
Generic placeholder image

Current Drug Metabolism

Editor-in-Chief

ISSN (Print): 1389-2002
ISSN (Online): 1875-5453

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

Modulation of the Drug Resistance by Platonia insignis Mart. Extract, Ethyl Acetate Fraction and Morelloflavone/Volkensiflavone (Biflavonoids) in Staphylococcus aureus Strains Overexpressing Efflux Pump Genes

Author(s): Andressa K.F. e Silva, Antonielly C. dos Reis, Emanuelly E.A. Pinheiro, Jonas N. de Sousa, Felipe A. de Alcântara Oliveira, Arkellau K.S. Moura, José de Sousa L. Neto, Antonia M. das Graças L. Citó, José P. Siqueira-Júnior, Glenn W. Kaatz and Humberto M. Barreto*

Volume 22, Issue 2, 2021

Published on: 23 May, 2020

Page: [114 - 122] Pages: 9

DOI: 10.2174/1389200221666200523155617

Price: $65

Abstract

Background: Microbial resistance to antibiotics is a global public health problem, which requires urgent attention. Platonia insignis is a native species from the eastern Brazilian Amazon, used in the treatment of burns and wounds.

Objectives: To evaluate the antimicrobial activity of the hydroalcoholic extract of P. insignis (PIHA), the ethyl acetate fraction (PIAE), and its subfraction containing a mixture of biflavonoids (BF). Moreover, the effect of these natural products on the antibiotic activity against S. aureus strains overexpressing efflux pump genes was also evaluated.

Methods: Minimal inhibitory concentrations were determined against different species of microorganisms. To evaluate the modulatory effect on the Norfloxacin-resistance, the MIC of this antibiotic was determined in the absence and presence of the natural products at subinhibitory concentrations. Inhibition of the EtBr efflux assays were conducted in the absence or presence of natural products.

Results: PIHA showed a microbicidal effect against S. aureus and C. albicans, while PIAE was bacteriostatic for S. aureus. PIAE and BF at subinhibitory concentrations were able to reduce the MIC of Norfloxacin acting as modulating agents. BF was able to inhibit the efflux of EtBr efflux in S. aureus strains overexpressing specific efflux pump genes.

Conclusion: P. inignisis, a source of efflux pump inhibitors, including volkensiflavone and morelloflavone, which were able to potentiate the Norfloxacin activity by NorA inhibition, being also able to inhibit QacA/B, TetK and MsrA. Volkensiflavone and morelloflavone could be used as an adjuvant in the antibiotic therapy of multidrug resistant S. aureus strains overexpressing efflux pumps.

Keywords: Platonia insignis, antimicrobial activity, resistance to antibiotics, efflux pumps, Staphylococcus aureus, modulation of the drug resistance.

« Previous Next »
Graphical Abstract

[1]
Taylor, A.R. Methicillin-resistant Staphylococcus aureus infections. Prim. Care, 2013, 40(3), 637-654.
[http://dx.doi.org/10.1016/j.pop.2013.06.002] [PMID: 23958361]
[2]
Prestinaci, F.; Pezzotti, P.; Pantosti, A. Antimicrobial resistance: a global multifaceted phenomenon. Pathog. Glob. Health, 2015, 109(7), 309-318.
[http://dx.doi.org/10.1179/2047773215Y.0000000030] [PMID: 26343252]
[3]
Ragheb, M.N.; Thomason, M.K.; Hsu, C.; Nugent, P.; Gage, J.; Samadpour, A.N.; Kariisa, A.; Merrikh, C.N.; Miller, S.I.; Sherman, D.R.; Merrikh, H. Inhibiting the evolution of antibiotic resistance. Mol. Cell, 2019, 73(1), 157-165.e5.
[http://dx.doi.org/10.1016/j.molcel.2018.10.015] [PMID: 30449724]
[4]
Swietnicki, W. Recent advances in antibacterial drug development. Int. J. Recent Sci. Res., 2018, 9, 26501-26505.
[http://dx.doi.org/10.24327/ijrsr.2018.0905.207]
[5]
Idsa, Infectious Diseases Society of America. The 10×'20 initiative: pursuing a global commitment to develop 10 new antibacterial drugs by 2020. Clin. Infect. Dis., 2010, 50, 1081-1083.
[http://dx.doi.org/10.1086/652237] [PMID: 20214473]
[6]
Pinto, C.P.; Rodrigues, V.D.; Pinto, F.P.; Pinto, R.P.; Uetanabaro, A.P.T.; Pinheiro, C.S.R.; Gadea, S.F.M.; Silva, T.R.S.; Lucchese, A.M. Antimicrobial activity of Lippia species from the Brazilian semiarid region tradionally used as antiseptic and anti-infective agents. Evid. Based Complement, 2013, 2013, 1-5.
[http://dx.doi.org/10.1155/2013/614501]
[7]
Coutinho, H.D.; Costa, J.G.; Lima, E.O.; Falcão-Silva, V.S. SiqueiraJúnior, J. P. Herbal therapy associated with antibiotic therapy: potentiation of the antibiotic activity against methicillin-resistant Staphylococcus aureus by Turneraulmifolia L. BMC Complement. Altern. Med., 2009, 9, 13.
[http://dx.doi.org/10.1186/1472-6882-9-13] [PMID: 19426487]
[8]
Samoilova, Z.; Muzyka, N.; Lepekhina, E.; Oktyabrsky, O.; Smirnova, G. Medicinal plant extracts can variously modify biofilm formation in Escherichia coli. Antonie van Leeuwenhoek, 2014, 105(4), 709-722.
[http://dx.doi.org/10.1007/s10482-014-0126-3] [PMID: 24500005]
[9]
Costa, L.M.; de Macedo, E.V.; Oliveira, F.A.A.; Ferreira, J.H.L.; Gutierrez, S.J.C.; Peláez, W.J.; Lima, F.C.; de Siqueira Júnior, J.P.; Coutinho, H.D.; Kaatz, G.W.; de Freitas, R.M.; Barreto, H.M. Inhibition of the NorA efflux pump of Staphylococcus aureus by synthetic riparins. J. Appl. Microbiol., 2016, 121(5), 1312-1322.
[http://dx.doi.org/10.1111/jam.13258] [PMID: 27537678]
[10]
Barreto, H.M.; Fontinele, F.C.; Oliveira, A.P.; Arcanjo, D.D.R.; Santos, B.H.C.; Abreu, A.P.L. Phytochemical prospection and modulation of antibiotic activity in vitro by Lippia origanoides HBK in methicillin resistant Staphylococcus aureus. BioMed Res. Int., 2014, 2014305610
[http://dx.doi.org/10.1155/2014/305610]
[11]
Rath, S.K.; Singh, S.; Kumar, S.; Wani, N.A.; Rai, R.; Koul, S.; Khan, I.A.; Sangwan, P.L. Synthesis of amides from (E)-3-(1-chloro-3,4-dihydronaphthalen-2-yl)acrylic acid and substituted amino acid esters as NorA efflux pump inhibitors of Staphylococcus aureus. Bioorg. Med. Chem., 2019, 27(2), 343-353.
[http://dx.doi.org/10.1016/j.bmc.2018.12.008] [PMID: 30552006]
[12]
Gobbo-Neto, L.; Lopes, N.P. Plantasmedicinais: fatores de influência no conteúdo de metabólitossecundários. Quim. Nova, 2007, 30, 374.
[http://dx.doi.org/10.1590/S0100-40422007000200026]
[13]
Ostrosky, E.A.; Mizumoto, M.K.; Lima, M.E.; Kaneko, T.M.; Nishikawa, S.O.; Freitas, B.R. Métodos para avaliação da atividadeantimicrobiana e determinação da concentraçãomínimainibitória (CMI) de plantasmedicinais. Rev. Bras. Farmacogn., 2008, 18, 301-307.
[http://dx.doi.org/10.1590/S0102-695X2008000200026]
[14]
Braga, R. Plantas do Nordeste: especialmente do Ceará; EditoraUniversitaria da UFRN, 1960.
[15]
Cavalcante, P.B. Frutascomestíveis da Amazônia. Belém: CNPq/ MuseuParaenseEmílioGoeldi, 6th ed; , 1996.
[16]
Nascimento, W.M.O.; De Carvalho, J.E.U.; Müller, C.H. Ocorrência e distribuiçãogeográfica do bacurizeiro. EmbrapaAmazônia Oriental-Artigoemperiódicoindexado; ALICE, 2007.
[17]
Costa Júnior, J.S.; de Almeida, A.A.; de Barros Falcão Ferraz, A.; Rossatto, R.R.; Silva, T.G.; Silva, P.B.; Militão, G.C. das Graças Lopes Citó, A.M.; Santana, L.C.; de Amorim Carvalho, F.A.; Freitas, R.M. Cytotoxic and leishmanicidal properties of garcinielliptone FC, a prenylated benzophenone from Platonia insignis. Nat. Prod. Res., 2013, 27(4-5), 470-474.
[http://dx.doi.org/10.1080/14786419.2012.695363] [PMID: 22708546]
[18]
Costa Júnior, J.S.; Feitosa, C.M.; Cito, A.D.G.L.; Freitas, R.M.; Henriques, J.A.P.; Saffi, J. Evaluation of effects of ethanolic extract from Platoniainsignis Mart. on pilocarpine-induced seizures. J. Biol. Sci., 2010, 10, 747-753.
[http://dx.doi.org/10.3923/jbs.2010.747.753]
[19]
Costa Júnior, J.S.; Ferraz, A.B.F.; Barros Filho, B.A.; Feitosa, C.M.; Citó, A.M.G.L.; Freitas, R.M.; Saffi, J. Evaluation of antioxidant effects in vitro of garcinielliptone FC (GFC) isolated from Platonia insignis Mart. J. Med. Plants Res., 2011, 5, 293-299.
[20]
Markham, P.N.; Westhaus, E.; Klyachko, K.; Johnson, M.E.; Neyfakh, A.A. Multiple novel inhibitors of the NorA multidrug transporter of Staphylococcus aureus. Antimicrob. Agents Chemother., 1999, 43(10), 2404-2408.
[http://dx.doi.org/10.1128/AAC.43.10.2404] [PMID: 10508015]
[21]
Neyfakh, A.A.; Borsch, C.M.; Kaatz, G.W. Fluoroquinolone resistance protein NorA of Staphylococcus aureus is a multidrug efflux transporter. Antimicrob. Agents Chemother., 1993, 37(1), 128-129.
[http://dx.doi.org/10.1128/AAC.37.1.128] [PMID: 8431010]
[22]
Kaatz, G.W.; Seo, S.M.; O’Brien, L.; Wahiduzzaman, M.; Foster, T.J. Evidence for the existence of a multidrug efflux transporter distinct from NorA in Staphylococcus aureus. Antimicrob. Agents Chemother., 2000, 44(5), 1404-1406.
[http://dx.doi.org/10.1128/AAC.44.5.1404-1406.2000] [PMID: 10770791]
[23]
Houghton, P.J.; Howes, M.J.; Lee, C.C.; Steventon, G. Uses and abuses of in vitro tests in ethnopharmacology: visualizing an elephant. J. Ethnopharmacol., 2007, 110(3), 391-400.
[http://dx.doi.org/10.1016/j.jep.2007.01.032] [PMID: 17317057]
[24]
French, G.L. Bactericidal agents in the treatment of MRSA infections--the potential role of daptomycin. J. Antimicrob. Chemother., 2006, 58(6), 1107-1117.
[http://dx.doi.org/10.1093/jac/dkl393] [PMID: 17040922]
[25]
Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol. Mol. Biol. Rev., 2003, 67(4), 593-656.
[http://dx.doi.org/10.1128/MMBR.67.4.593-656.2003] [PMID: 14665678]
[26]
Zhang, J.; Sun, Y.; Wang, Y.; Lu, M.; He, J.; Liu, J.; Chen, Q.; Zhang, X.; Zhou, F.; Wang, G.; Sun, X. Non-antibiotic agent ginsenoside 20(S)-Rh2 enhanced the antibacterial effects of ciprofloxacin in vitro and in vivo as a potential NorA inhibitor. Eur. J. Pharmacol., 2014, 740, 277-284.
[http://dx.doi.org/10.1016/j.ejphar.2014.07.020] [PMID: 25054686]
[27]
Gibbons, S.; Udo, E.E. The effect of reserpine, a modulator of multidrug efflux pumps, on the in vitro activity of tetracycline against clinical isolates of methicillin resistant Staphylococcus aureus (MRSA) possessing the tet(K) determinant. Phytother. Res., 2000, 14(2), 139-140.
[http://dx.doi.org/10.1002/(SICI)1099-1573(200003)14:2<139:AID-PTR608>3.0.CO;2-8] [PMID: 10685116]
[28]
Brown, M.H.; Skurray, R.A. Staphylococcal multidrug efflux protein QacA. J. Mol. Microbiol. Biotechnol., 2001, 3(2), 163-170.
[PMID: 11321569]
[29]
Kaatz, G.W.; Seo, S.M.; Ruble, C.A. Efflux-mediated fluoroquinolone resistance in Staphylococcus aureus. Antimicrob. Agents Chemother., 1993, 37(5), 1086-1094.
[http://dx.doi.org/10.1128/AAC.37.5.1086] [PMID: 8517696]
[30]
Ross, J.I.; Farrell, A.M.; Eady, E.A.; Cove, J.H.; Cunliffe, W.J. Characterisation and molecular cloning of the novel macrolide-streptogramin B resistance determinant from Staphylococcus epidermidis. J. Antimicrob. Chemother., 1989, 24(6), 851-862.
[http://dx.doi.org/10.1093/jac/24.6.851] [PMID: 2559912]
[31]
Shriram, V.; Khare, T.; Bhagwat, R.; Shukla, R.; Kumar, V. Inhibiting bacterial drug efflux pumps via phyto-therapeutics to combat threatening antimicrobial resistance. Front. Microbiol., 2018, 9, 2990.
[http://dx.doi.org/10.3389/fmicb.2018.02990] [PMID: 30619113]
[32]
Dos Santos, J.F.S.; Tintino, S.R.; de Freitas, T.S.; Campina, F.F. de A Menezes, I.R.; Siqueira-Júnior, J.P.; Coutinho, H.D.M.; Cunha, F.A.B. In vitro e in silico evaluation of the inhibition of Staphylococcus aureus efflux pumps by caffeic and gallic acid. Comp. Immunol. Microbiol. Infect. Dis., 2018, 57, 22-28.
[http://dx.doi.org/10.1016/j.cimid.2018.03.001] [PMID: 30017074]
[33]
Tintino, S.R.; Oliveira-Tintino, C.D.; Campina, F.F.; Silva, R.L. Costa, Mdo.S.; Menezes, I.R.; Calixto-Júnior, J.T.; Siqueira-Junior, J.P.; Coutinho, H.D.; Leal-Balbino, T.C.; Balbino, V.Q. Evaluation of the tannic acid inhibitory effect against the NorA efflux pump of Staphylococcus aureus. Microb. Pathog., 2016, 97, 9-13.
[http://dx.doi.org/10.1016/j.micpath.2016.04.003] [PMID: 27057677]
[34]
Braga Ribeiro, A.M.; Sousa, J.N.; Costa, L.M.; Oliveira, F.A.A.; Dos Santos, R.C.; Silva Nunes, A.S.; da Silva, W.O.; Marques Cordeiro, P.J.; de Sousa Lima Neto, J.; de Siqueira-Júnior, J.P.; Kaatz, G.W.; Barreto, H.M.; de Oliveira, A.P. Antimicrobial activity of Phyllanthus amarus. Schumach & Thonn and inhibition of the NorA efflux pump of Staphylococcus aureus by Phyllanthin. Microb. Pathog., 2019, 130, 242-246.
[http://dx.doi.org/10.1016/j.micpath.2019.03.012] [PMID: 30876871]
[35]
Joshi, P.; Singh, S.; Wani, A.; Sharma, S.; Jain, S.K.; Singh, B. Osthol and curcumin as inhibitors of human Pgp and multidrug efflux pumps of Staphylococcus aureus: reversing the resistance against frontline antibacterial drugs. MedChemComm, 2014, 5, 1540-1547.
[http://dx.doi.org/10.1039/C4MD00196F]
[36]
Espinoza, J.; Urzúa, A.; Sanhueza, L.; Walter, M.; Fincheira, P.; Muñoz, P.; Mendoza, L.; Wilkens, M. Essential oil, extracts, and sesquiterpenes obtained from the heartwood of Pilgerodendron uviferum act as potential inhibitors of the Staphylococcus aureus NorA multidrug efflux pump. Front. Microbiol., 2019, 10, 337.
[http://dx.doi.org/10.3389/fmicb.2019.00337] [PMID: 30863385]
[37]
Miladi, H.; Zmantar, T.; Chaabouni, Y.; Fedhila, K.; Bakhrouf, A.; Mahdouani, K.; Chaieb, K. Antibacterial and efflux pump inhibitors of thymol and carvacrol against food-borne pathogens. Microb. Pathog., 2016, 99, 95-100.
[http://dx.doi.org/10.1016/j.micpath.2016.08.008] [PMID: 27521228]
[38]
Coêlho, M.L.; Ferreira, J.H.L. SiqueiraJúnior J.P.; Kaatz G.W; Barreto H.M.; Cavalcante A.A.C.M. Inhibition of the NorA multi-drug transporter b oxygenated monoterpenes. Microb. Pathog., 2016, 99, 173-177.
[http://dx.doi.org/10.1016/j.micpath.2016.08.026] [PMID: 27565089]
[39]
Roy, S.K.; Kumari, N.; Pahwa, S.; Agrahari, U.C.; Bhutani, K.K.; Jachak, S.M.; Nandanwar, H. NorA efflux pump inhibitory activity of coumarins from Mesua ferrea. Fitoterapia, 2013, 90, 140-150.
[http://dx.doi.org/10.1016/j.fitote.2013.07.015] [PMID: 23892000]
[40]
Kalia, N.P.; Mahajan, P.; Mehra, R.; Nargotra, A.; Sharma, J.P.; Koul, S.; Khan, I.A. Capsaicin, a novel inhibitor of the NorA efflux pump, reduces the intracellular invasion of Staphylococcus aureus. J. Antimicrob. Chemother., 2012, 67(10), 2401-2408.
[http://dx.doi.org/10.1093/jac/dks232] [PMID: 22807321]
[41]
Sabatini, S.; Gosetto, F.; Manfroni, G.; Tabarrini, O.; Kaatz, G.W.; Patel, D.; Cecchetti, V. Evolution from a natural flavones nucleus to obtain 2-(4-Propoxyphenyl)quinoline derivatives as potent inhibitors of the S. aureus NorA efflux pump. J. Med. Chem., 2011, 54(16), 5722-5736.
[http://dx.doi.org/10.1021/jm200370y] [PMID: 21751791]
[42]
Maia, G.L.D.A. Falcão-Silva, Vdos.S.; Aquino, P.G.V.; de Araújo-Júnior, J.X.; Tavares, J.F.; da Silva, M.S.; Rodrigues, L.C.; de Siqueira-Júnior, J.P.; Barbosa-Filho, J.M. Flavonoids from Praxelis clematidea R.M. King and Robinson modulate bacterial drug resistance. Molecules, 2011, 16(6), 4828-4835.
[http://dx.doi.org/10.3390/molecules16064828] [PMID: 21666549]

Rights & Permissions Print Cite
Article Metrics
105
© 2024 Bentham Science Publishers | Privacy Policy