Abstract
Algal alkaloids are widely used for their pharmacological properties as antimicrobial agents. This study determined the antibacterial activities of algal alkaloid-rich extracts against isolates of multidrug-resistant Staphylococcus aureus and enterohaemorrhagic Escherichia coli (EHEC) O157, as well as the probable mode of action underlying their antibacterial effect. The total alkaloids were extracted from two Libyan brown algae, namely Sargassum hornschuchii and Cystoseira compressa and tested against six different isolates from the bacteria mentioned above using the agar-well diffusion method, and their mode of action on isolates was evaluated by several bacterial physiological indicators, including intracellular potassium ion efflux and nucleotide leakage. Also, the extracts' hemolytic activity was assessed as an indicator of their cytotoxicity on red blood cells. Although not to the same extent, both alkaloid extracts presented antibacterial activities against all tested isolates with no evidence of bacterial regrowth. The alkaloid extract from S. hornschuchii exerted the best effect on bacteria growth with minimum inhibitory concentration values ranging between 125 and 500 mg/mL. The results showed that the alkaloid extracts significantly induced a distinct release of nucleotide and potassium ions out of the cell membrane, indicating that they cause a change in the fluidity or permeability or both of the cell membrane. Moreover, the results revealed that there were very low cytotoxic effects. Therefore, algal alkaloids may contribute to the development of potential antibacterial agents in the future.
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Bhakuni, D.S.; Rawat, D.S.: Bioactive Marine Natural Products. Springer, Berlin (2006)
Saadaoui, I.; Rasheed, R.; Abdulrahman, N.; Bounnit, T.; Cherif, M.; Al Jabri, H.; Mraiche, F.: Algae-derived bioactive compounds with anti-lung cancer potential. Mar. Drugs 18, 197 (2020)
Kaleagasioglu, F.; Güven, K.C.; Sezik, E.; Erdugan, H.; Coban, B.: Pharmacology of macroalgae alkaloids. In: Natural Products, pp. 1203–1216. Berlin, Heidelberg (2013)
Gul, W.; Hamann, M.T.: Indole alkaloid marine natural products: an established source of cancer drug leads with considerable promise for the control of parasitic, neurological and other diseases. Life Sci. 78, 442–453 (2005)
Güven, K.C.; Percot, A.; Sezik, E.: Alkaloids in marine algae. Mar. Drugs. 8, 269–284 (2010)
Souza, C.R.; Bezerra, W.P.; Souto, J.T.: Marine alkaloids with anti-inflammatory activity: current knowledge and future perspectives. Mar. Drugs. 18, 147 (2020)
Alghazeer, R.; Whida, F.; Abduelrhman, E.; Gammoudi, F.; Azwai, S.: Screening of antibacterial activity in marine green, red and brown macroalgae from the western coast of Libya. Nat. Sci. 5, 7–14 (2013)
Xu, X.; Zhu, Y.; Gao, W.; Kong, C.: Agricultural lead compounds from Laurencia majuscula. Proc. Int. Forum Green Chem. Sci. Eng. Process Syst. Eng. 2006, 538–541 (2006)
Rehman, S.; Khan, H.: Advances in antioxidant potential of natural alkaloids. Curr. Bioact. Compd. 13, 101–108 (2017)
Liu, M.; Xu, H.; Lin, X.: Pharmacological profile of bromophenols derived from marine organisms. Encycl. Mar. Biotechnol. 3, 1619–1639 (2020)
Gross, H.; Goeger, D.E.; Hills, P.; Mooberry, S.L.; Ballantine, D.L.; Murray, T.F.; Valeriote, F.A.; Gerwick, W.H.: Lophocladines, bioactive alkaloids from the red alga Lophocladia sp. J. Nat. Prod. 69, 640–644 (2006)
Nijampatnam, B.; Dutta, S.; Velu, S.E.: Recent developments in the isolation, synthesis, and bioactivities of bispyrroloquinone alkaloids of marine origin. Chin. J. Nat. Med. 13, 561 (2015)
Saudagar, R.B.; Saokar, S.: Anti-inflammatory natural compounds from herbal and marine origin. J. Drug Deliv. Ther. 9, 669–672 (2019)
Luqman, A.; Nega, M.; Nguyen, M.T.; Ebner, P.; Götz, F.: SadA-expressing staphylococci in the human gut show increased cell adherence and internalization. Cell Rep. 22, 535–545 (2018)
Melander, R.J.; Liu, H.B.; Stephens, M.D.; Bewley, C.A.; Melander, C.: Marine sponge alkaloids as a source of anti-bacterial adjuvants. Bioorg. Med. Chem. Lett. 26, 5863–5866 (2016)
Fathima, A.; Rao, J.R.: Selective toxicity of Catech in—a natural flavonoid towards bacteria. Appl. Microbiol. Biotechnol. 100, 6395–6402 (2016)
Gafur, A.; Sukamdani, G.Y.; Kristi, N.; Maruf, A.; Xu, J.; Chen, X.; Wang, G.; Ye, Z.: From bulk to nano-delivery of essential phytochemicals: recent progress and strategies for antibacterial resistance. J. Mater. Chem. B. 8, 9825–9835 (2020)
Maurya, A.; Dwivedi, G.R.; Darokar, M.P.; Srivastava, S.K.: Antibacterial and synergy of clavine alkaloid lysergol and its derivatives against nalidixic acid-resistant Escherichia coli. Chem. Biol. Drug Des. 81, 484–490 (2013)
Mullin, S.; Mani, N.; Grossman, T.H.: Inhibition of antibiotic efflux in bacteria by the novel multidrug resistance inhibitors biricodar (VX-710) and timcodar (VX-853). Antimicrob. Agents Chemother. 48, 4171–4176 (2004)
Mabhiza, D.; Chitemerere, T.; Mukanganyama, S.: Antibacterial properties of alkaloid extracts from Callistemon citrinus and Vernonia adoensis against Staphylococcus aureus and Pseudomonas aeruginosa. Int. J. Med. Chem. 2016, 1–7 (2016)
Alghazeer, R.; Elmansori, A.; Sidati, M.; Gammoudi, F.; Azwai, S.; Naas, H.; Garbaj, A.; Eldaghayes, I.: In vitro antibacterial activity of flavonoid extracts of two selected libyan algae against multi-drug resistant bacteria isolated from food products. J. Biosci. Med. 5, 26 (2017)
Hadi, S.; Bremner, J.B.: Initial studies on alkaloids from Lombok medicinal plants. Molecules 6, 117–129 (2001)
Garbaj, A.M.; Awad, E.M.; Azwai, S.M.; Abolghait, S.K.; Naas, H.T.; Moawad, A.A.; Gammoudi, F.T.; Barbieri, I.; Eldaghayes, I.M.: Enterohemorrhagic Escherichia coli O157 in milk and dairy products from Libya: isolation and molecular identification by partial sequencing of 16S rDNA. Vet. World 9, 1184 (2016)
Naas, H.T.; Edarhoby, R.A.; Garbaj, A.M.; Azwai, S.M.; Abolghait, S.K.; Gammoudi, F.T.; Moawad, A.A.; Barbieri, I.; Eldaghayes, I.M.: Occurrence, characterization, and antibiogram of Staphylococcus aureus in meat, meat products, and some seafood from Libyan retail markets. Vet. World. 12, 925 (2019)
Azwai, S.M.; Alfallani, E.A.; Abolghait, S.K.; Garbaj, A.M.; Naas, H.T.; Moawad, A.A.; Gammoudi, F.T.; Rayes, H.M.; Barbieri, I.; Eldaghayes, I.M.: Isolation and molecular identification of Vibrio spp. by sequencing of 16S rDNA from seafood, meat and meat products in Libya. Open Vet. J. 6, 36–43 (2016)
Manilal, A.; Sujith, S.; Kiran, G.S.; Selvin, J.; Shakir, C.; Gandhimathi, R.; Panikkar, M.V.N.: Biopotentials of seaweeds collected from southwest coast of India. J. Mar. Sci. Technol. 17, 67–73 (2009)
Daud, A.; Gallo, A.; Riera, A.S.: Antimicrobial properties of Phrygilanthus acutifolius. J. Ethnopharmacol. 99, 193–197 (2005)
Spencer, J.F.; de Spencer, A.L.R.: Public Health Microbiology: Methods and Protocols, Vol. 268. Springer, Berlin (2004)
Hao, G.; Shi, Y.H.; Tang, Y.L.; Le, G.W.: The membrane action mechanism of analogs of the antimicrobial peptide Buforin 2. Peptides 30, 1421–1427 (2009)
Tang, Y.L.; Shi, Y.H.; Zhao, W.; Hao, G.; Le, G.W.: Insertion mode of a novel anionic antimicrobial peptide MDpep5 (Val-Glu-Ser-Trp-Val) from Chinese traditional edible larvae of housefly and its effect on surface potential of bacterial membrane. J. Pharm. Biomed. Anal. 48, 1187–1194 (2008)
Da Silva, E.; Shahgaldian, P.; Coleman, A.W.: Haemolytic properties of some water-soluble para-sulphonato-calix-[n]-arenes. Int. J. Pharm. 273, 57–62 (2004)
Shannon, E.; Abu-Ghannam, N.: Antibacterial derivatives of marine algae: an overview of pharmacological mechanisms and applications. Mar. Drugs 14, 81 (2016)
Mickymaray, S.; Alturaiki, W.: Antifungal efficacy of marine macroalgae against fungal isolates from bronchial asthmatic cases. Molecules 23, 3032 (2018)
Kim, S.-K.; Vo, T.-S.; Ngo, D.-H.: Potential application of marine algae as antiviral agents in medicinal foods. Adv. Food Nutr. Res. 64, 245–254 (2011)
Lunagariya, J.; Bhadja, P.; Zhong, S.; Vekariya, R.; Xu, S.: Marine natural product bis-indole alkaloid caulerpin: chemistry and biology. Mini. Rev. Med. Chem. 19, 751–761 (2019)
Leandro, A.; Pereira, L.; Gonçalves, A.M.: Diverse applications of marine macroalgae. Mar. Drugs 18, 17 (2020)
Ramawat, K.G.; Mérillon, J.-M.: Natural products: phytochemistry, botany and metabolism of alkaloids, phenolics and terpenes. Springer, Berlin (2013)
Abad, M.; Bedoya, L.; Bermejo, P.: Marine compounds and their antimicrobial activities. Sci Against Microb Pathog Commun Curr Res Technol Adv 51, 1293–1306 (2011)
Ebada, S.S.; Lin, W.; Proksch, P.: Bioactive sesterterpenes and triterpenes from marine sponges: occurrence and pharmacological significance. Mar. Drugs 8, 313–346 (2010)
Kurhekar, J.V.: Chapter 17 - Antimicrobial lead compounds from marine plants. In: Egbuna, C., Kumar, S., Ifemeje, J.C., Ezzat, S.M., Kaliyaperumal, S. (eds.) Phytochemicals as Lead Compounds for New Drug Discovery. Elsevier (2020)
Chen, C.Z.; Cooper, S.L.: Interactions between dendrimer biocides and bacterial membranes. Biomaterials 23, 3359–3368 (2002)
Tüney, İ; Cadirci, B.H.; Ünal, D.; Sukatar, A.: Antimicrobial activities of the extracts of marine algae from the coast of Urla (Izmir, Turkey). Turk. J. Biol. 30, 171–175 (2006)
Aziz, E.; Batool, R.; Khan, M.U.; Rauf, A.; Akhtar, W.; Heydari, M.; Rehman, S.; Shahzad, T.; Malik, A.; Mosavat, S.H.; Plygun, S.: An overview on red algae bioactive compounds and their pharmaceutical applications. J. Complement. Integr. Med. 17, 4 (2020)
Casciaro, B.; Mangiardi, L.; Cappiello, F.; Romeo, I.; Loffredo, M.R.; Iazzetti, A.; Calcaterra, A.; Goggiamani, A.; Ghirga, F.; Mangoni, M.L.; Botta, B.: Naturally-occurring alkaloids of plant origin as potential antimicrobials against antibiotic-resistant infections. Molecules 25, 3619 (2020)
Gajdács, M.: The concept of an ideal antibiotic: implications for drug design. Molecules 24, 892 (2019)
French, G.L.: Bactericidal agents in the treatment of MRSA infections—the potential role of daptomycin. J. Antimicrob. Chemother. 58, 1107–1117 (2006)
Otshudi, A.L.; Apers, S.; Pieters, L.; Claeys, M.; Pannecouque, C.; De Clercq, E.; Van Zeebroeck, A.; Lauwers, S.; Frederich, M.; Foriers, A.: Biologically active bisbenzylisoquinoline alkaloids from the root bark of Epinetrum villosum. J. Ethnopharmacol. 102, 89–94 (2005)
Kuete, V.; Wansi, J.D.; Mbaveng, A.T.; Sop, M.K.; Tadjong, A.T.; Beng, V.P.; Etoa, F.X.; Wandji, J.; Meyer, J.M.; Lall, N.: Antimicrobial activity of the methanolic extract and compounds from Teclea afzelii (Rutaceae). S. Afr. J. Bot. 74, 572–576 (2008)
Alhanout, K.; Malesinki, S.; Vidal, N.; Peyrot, V.; Rolain, J.M.; Brunel, J.M.: New insights into the antibacterial mechanism of action of squalamine. J. Antimicrob. Chemother. 65, 1688–1693 (2010)
Tavares, L.D.C.; Zanon, G.; Weber, A.D.; Neto, A.T.; Mostardeiro, C.P.; Da Cruz, I.B.; Oliveira, R.M.; Ilha, V.; Dalcol, I.I.; Morel, A.F.: Structure-activity relationship of benzophenanthridine alkaloids from Zanthoxylum rhoifolium having antimicrobial activity. PLoS ONE 9, e97000 (2014)
Bezić, N.; Skočibušić, M.; Dunkić, V.; Radonić, A.: Composition and antimicrobial activity of Achillea clavennae L. essential oil. Phytother. Res. 17, 1037–1040 (2003)
Bajpai, V.K.: Antimicrobial bioactive compounds from marine algae: a mini review Indian. J. Geo Mar. Sci. 9, 1076–1085 (2016)
Tsuchiya, H.: Membrane interactions of phytochemicals as their molecular mechanism applicable to the discovery of drug leads from plants. Molecules 20, 18923–18966 (2015)
Mittal, R.P.; Jaitak, V.: Plant-derived natural alkaloids as new antimicrobial and adjuvant agents in existing antimicrobial therapy. Curr. Drug Targets. 20, 1409–1433 (2019)
Kittakoop, P.; Mahidol, C.; Ruchirawat, S.: Alkaloids as important scaffolds in therapeutic drugs for the treatments of cancer, tuberculosis, and smoking cessation. Curr. Top. Med. Chem. 14, 239–252 (2014)
Thawabteh, A.; Juma, S.; Bader, M.; Karaman, D.; Scrano, L.; Bufo, S.A.; Karaman, R.: The biological activity of natural alkaloids against herbivores, cancerous cells and pathogens. Toxins 11, 656 (2019)
Sawer, I.K.; Berry, M.I.; Ford, J.L.: The killing effect of cryptolepine on Staphylococcus aureus. Lett. Appl. Microbiol. 40, 24–29 (2005)
Cushnie, T.T.; Cushnie, B.; Lamb, A.J.: Alkaloids: an overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int. J. Antimicrob. Agents 44, 377–386 (2014)
Dassonneville, L.; Lansiaux, A.; Wattelet, A.; Wattez, N.; Mahieu, C.; Van Miert, S.; Pieters, L.; Bailly, C.: Cytotoxicity and cell cycle effects of the plant alkaloids cryptolepine and neocryptolepine: relation to drug-induced apoptosis. Eur. J. Pharmacol. 409, 9–18 (2000)
Lisgarten, J.N.; Coll, M.; Portugal, J.; Wright, C.W.; Aymami, J.: The antimalarial and cytotoxic drug cryptolepine intercalates into DNA at cytosine-cytosine sites. Nat. Struct. Biol. 9, 57–60 (2002)
Guittat, L.; Alberti, P.; Rosu, F.; Van Miert, S.; Thetiot, E.; Pieters, L.; Gabelica, V.; De Pauw, E.; Ottaviani, A.; Riou, J.F.; Mergny, J.L.: Interactions of cryptolepine and neocryptolepine with unusual DNA structures. Biochimie 85, 535–547 (2003)
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RA conceived, designed, and organized the study. SA, AMG, AA, SE, MS, EY, and MGK contributed to the conduct of the study. SA, AMG, AA, SE, AAE, GS, and WSA performed the experiments, RA, AAE, GS, and WSA analyzed the data. RA, SA, AMG, AA, SE, MS, EY, and MGK drafted the manuscript and critiqued the output for intellectual content. All authors discussed the results and commented on the manuscript.
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Alghazeer, R., Azwai, S., Garbaj, A.M. et al. Alkaloids Rich Extracts from Brown Algae Against Multidrug-Resistant Bacteria by Distinctive Mode of Action. Arab J Sci Eng 47, 179–188 (2022). https://doi.org/10.1007/s13369-021-05592-w
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DOI: https://doi.org/10.1007/s13369-021-05592-w