Lipopeptides: Powerful Antifungal Compounds Produced by Bacillus Species: A Review

Tahir Mahmood, Anam Moosa, Waseem Ahmad, Atta ur Rehman Khan, Javaria Malik, Muhammad Umar Shafiq, Michael Yousaf, Hammad Anwar, Muhammad Luqman, Zain Ul Abadin, Ghayor Abbas


Phytopathogens affect the crops each year and hurt the economy of the country. Researchers’ main concern is investigating biocontrol agents’ potential as alternative sources to combat diseases. The Bacillus genus produced various plant growth-promoting compounds useful for managing plant diseases. These agents are harmless to the environment and proven effective antagonists against pathogens. The lipopeptides extracted by Bacillus spp. are effective germ killers, and the most notable among them are iturins, surfactin, fengycin, bacillomycin, and plipastatin, which exhibit potent antibacterial action against a wide variety of phytopathogens. Lipopeptides are non-toxic, biodegradable, and friendly to the natural world. Different lipopeptides have been reviewed for their function and mechanism of action in biocontrol in literature. The purpose of this review is to analyze the previous and recent research work and the mechanisms that involved for the management of disease by lipopeptides produced by Bacillus genus


Bacillomycin; Fengycin; Iturin; Surfactin; Plipastatin; Secondary Metabolites; Antimicrobial; Biocontrol

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Abramovitch, R.B., Anderson, J.C., Martin, G.B., 2006. Bacterial elicitation and evasion of plant innate immunity. Nature Reviews Molecular Cell Biology 7(8), 601-611.

Akpa, E., Jacques, P., Wathelet, B., Paquot, M., Fuchs, R., Budzikiewicz, H., Thonart, P., 2001. Influence of culture conditions on lipopeptide production by Bacillus subtilis. Applied Biochemistry and Biotechnology 91(1), 551-561.

Bais, H.P., Fall, R., Vivanco, J.M., 2004. Biocontrol of Bacillus subtilis against infection of Arabidopsis roots by Pseudomonas syringae is facilitated by biofilm formation and surfactin production. Plant Physiology 134(1), 307-319.

Bais, H.P., Weir, T.L., Perry, L.G., Gilroy, S., Vivanco, J.M., 2006. The role of root exudates in rhizosphere interactions with plants and other organisms. Annual Review of Plant Biology 57, 233-266.

Ben Ayed, H., Hmidet, N., Béchet, M., Jacques, P., Nasri, M., 2017. Identification and natural functions of cyclic lipopeptides from Bacillus amyloliquefaciens An6. Engineering in Life Sciences 17(5), 536-544.

Berendsen, R.L., Pieterse, C.M., Bakker, P.A., 2012. The rhizosphere microbiome and plant health. Trends in Plant Science 17(8), 478-486.

Blée, E., 2002. Impact of phyto-oxylipins in plant defense. Trends in Plant Science 7(7), 315-322.

Calcott, M.J. and Ackerley, D.F., 2014. Genetic manipulation of non-ribosomal peptide synthetases to generate novel bioactive peptide products. Biotechnology Letters 36(12), 2407-2416.

Cawoy, H., Bettiol, W., Fickers, P., Ongena, M., 2011. Bacillus-based biological control of plant diseases. Pesticides in the modern world-pesticides use and management. InTech Open 273-302.

Chen, Q.Q., Liu, B., Wang, J.P., Che, J.M., Liu, G.H., Gong, H.Y., Guan, X., 2016. Anti-fungal lipopeptides produced by Bacillus siamensis FJAT-28592. Journal of Agricultural Biotechnology 24(2), 261-269.

Constantinescu, F., 2001. Extraction and identification of antifungal metabolites produced by some B. subtilis strains. Analele Institutului de Cercetari Pentru Cereale Protectia Plantelor 31, 17-23.

Cozzolino, M.E., Distel, J.S., García, P.A., Mascotti, M.L., Ayub, M.J., Benazzi, L.M., Silva, P.G., 2020. Control of postharvest fungal pathogens in pome fruits by lipopeptides from a Bacillus sp. isolate SL-6. Scientia Horticulturae 261, 108957.

Daniels, R., Vanderleyden, J., Michiels, J., 2004. Quorum sensing and swarming migration in bacteria. FEMS Microbiology Reviews 28(3), 261-289.

de Weert, S., Vermeiren, H., Mulders, I.H., Kuiper, I., Hendrickx, N., Bloemberg, G.V., Vanderleyden, J., De Mot, R., Lugtenberg, B.J., 2002. Flagella-driven chemotaxis towards exudate components is an important trait for tomato root colonization by Pseudomonas fluorescens. Molecular Plant-Microbe Interactions 15(11), 1173-1180.

Deng, Q., Wang, W., Sun, L., Wang, Y., Liao, J., Xu, D., Liu, Y., Ye, R., Gooneratne, R., 2017. A sensitive method for simultaneous quantitative determination of surfactin and iturin by LC-MS/MS. Analytical and Bioanalytical Chemistry 409(1), 179-191.

Dietel, K., Beator, B., Budiharjo, A., Fan, B., Borriss, R., 2013. Bacterial traits involved in colonization of Arabidopsis thaliana roots by Bacillus amyloliquefaciens FZB42. The Plant Pathology Journal 29(1), 59-66.

Emmert, E.A., Handelsman, J., 1999. Biocontrol of plant disease: a (Gram-) positive perspective. FEMS Microbiology Letters 171(1), 1-9.

Falardeau, J., Wise, C., Novitsky, L., Avis, T.J., 2013. Ecological and mechanistic insights into the direct and indirect antimicrobial properties of Bacillus subtilis lipopeptides on plant pathogens. Journal of Chemical Ecology 39, 869-878.

Fatima, R., Mahmood, T., Moosa, A., Aslam, M.N., Shakeel, M.T., Maqsood, A., Al‐Shehri, M., 2023. Bacillus thuringiensis CHGP12 uses a multifaceted approach for the suppression of Fusarium oxysporum f. sp. ciceris and to enhance the biomass of chickpea plants. Pest Management Science 79(1), 336-348.

Fravel, D.R., 2005. Commercialization and implementation of biocontrol. Annual Review of Phytopathology 43, 337-359.

Geissler, M., Oellig, C., Moss, K., Schwack, W., Henkel, M., Hausmann, R., 2017. High-performance thin-layer chromatography (HPTLC) for the simultaneous quantification of the cyclic lipopeptides Surfactin, Iturin A and Fengycin in culture samples of Bacillus species. Journal of Chromatography B 1044, 214-224.

Guardado-Valdivia, L., Tovar-Pérez, E., Chacón-López, A., López-García, U., Gutiérrez-Martínez, P., Stoll, A., Aguilera, S., 2018. Identification and characterization of a new Bacillus atrophaeus strain B5 as biocontrol agent of postharvest anthracnose disease in soursop (Annona muricata) and avocado (Persea americana). Microbiological Research 210, 26-32.

Honma, M., Tanaka, K., Konno, K., Tsuge, K., Okuno, T., Hashimoto, M., 2012. Termination of the structural confusion between plipastatin A1 and fengycin IX. Bioorganic and Medicinal Chemistry 20(12), 3793-3798.

Hussein, W., Awad, H., Fahim, S., 2016. Systemic resistance induction of tomato plants against ToMV virus by surfactin produced from Bacillus subtilis BMG02. American Journal of Microbiological Research 4(5), 153-158.

Jacques, P., Hbid, C., Destain, J., Razafindralambo, H., Paquot, M., De Pauw, E., Thonart, P., 1999. Optimization of biosurfactant lipopeptide production from Bacillus subtilis S499 by Plackett-Burman design. Applied Biochemistry and Biotechnology 77(1-3), 223-233.

Janisiewicz, W.J., Korsten, L., 2002. Biological control of postharvest diseases of fruits. Annual Review of Phytopathology 40(1), 411-441.

Jasim, B., Sreelakshmi, S., Mathew, J., Radhakrishnan, E.K., 2016. Identification of endophytic Bacillus mojavensis with highly specialized broad spectrum antibacterial activity. 3 Biotech 6(2), 187.

Jourdan, E., Henry, G., Duby, F., Dommes, J., Barthelemy, J. P., Thonart, P., Ongena, M.A.R.C., 2009. Insights into the defense-related events occurring in plant cells following perception of surfactin-type lipopeptide from Bacillus subtilis. Molecular Plant-Microbe Interactions 22(4), 456-468.

Kamal, M. M., Savocchia, S., Lindbeck, K. D., & Ash, G. J. (2017). Rapid marker-assisted selection of antifungal Bacillus species from the canola rhizosphere. Plant Gene, 11, 23-30.

Kim, S.Y., Kim, J.Y., Kim, S.H., Bae, H.J., Yi, H., Yoon, S.H., Koo, B.S., Kwon, M., Cho, J.Y., Lee, C.E., Hong, S., 2007. Surfactin from Bacillus subtilis displays anti‐proliferative effect via apoptosis induction, cell cycle arrest and survival signaling suppression. FEBS Letters 581(5), 865-871.

Kinsinger, R.F., Shirk, M.C., Fall, R., 2003. Rapid surface motility in Bacillus subtilis is dependent on extracellular surfactin and potassium ion. Journal of Bacteriology 185(18), 5627-5631.

Kloepper, J.W., Ryu, C.M., Zhang, S., 2004. Induced systemic resistance and promotion of plant growth by Bacillus spp. Phytopathology 94(11), 1259-1266.

Koumoutsi, A., Chen, X.H., Henne, A., Liesegang, H., Hitzeroth, G., Franke, P., Vater, J., Borriss, R., 2004. Structural and functional characterization of gene clusters directing nonribosomal synthesis of bioactive cyclic lipopeptides in Bacillus amyloliquefaciens strain FZB42. Journal of Bacteriology 186(4), 1084-1096.

Kowall, M., Vater, J., Kluge, B., Stein, T., Franke, P., Ziessow, D., 1998. Separation and characterization of surfactin isoforms produced by Bacillus subtilis OKB 105. Journal of Colloid and Interface Science 204(1), 1-8.

Kracht, M., Rokos, H., Özel, M., Kowall, M., Pauli, G., Vater, J., 1999. Antiviral and hemolytic activities of surfactin isoforms and their methyl ester derivatives. The Journal of Antibiotics 52(7), 613-619.

Leclère, V., Marti, R., Béchet, M., Fickers, P., Jacques, P., 2006. The lipopeptides mycosubtilin and surfactin enhance spreading of Bacillus subtilis strains by their surface-active properties. Archives of Microbiology 186(6), 475-483.

Li, X., Zhang, Y., Wei, Z., Guan, Z., Cai, Y., Liao, X., 2016. Antifungal activity of isolated Bacillus amyloliquefaciens SYBC H47 for the biocontrol of peach gummosis. PloS One 11(9), e0162125.

Liu, Q., Shen, Q., Bian, X., Chen, H., Fu, J., Wang, H., ... & Zhang, Y. (2016). Simple and rapid direct cloning and heterologous expression of natural product biosynthetic gene cluster in Bacillus subtilis via Red/ET recombineering. Scientific reports, 6(1), 34623.

Lugtenberg, B.J., Dekkers, L., Bloemberg, G.V., 2001. Molecular determinants of rhizosphere colonization by Pseudomonas. Annual Review of Phytopathology 39(1), 461-490.

Maalik, S., Moosa, A., Zulfiqar, F., Aslam, M.N., Mahmood, T., Siddique, K.H., 2023. Endophytic Bacillus atrophaeus CHGP13 and salicylic acid inhibit blue mold of lemon by regulating defense enzymes. Frontiers in Microbiology 14, 1184297.

Maget-Dana, R., Ptak, M., 1990. Iturin lipopeptides: interactions of mycosubtilin with lipids in planar membranes and mixed monolayers. Biochimica et Biophysica Acta (BBA)-Biomembranes 1023(1), 34-40.

Mahmood, T., Fatima, R., Maalik, S., 2022. Lipopeptide powerful antifungal weapons produced by Bacillus species. Plant Bulletin 1, 1-13.

Nazari, F., Safaie, N., Soltani, B.M., Shams-Bakhsh, M., Sharifi, M., 2017. The effect of Bacillus subtilis producing Surfactin in ROS production and transformation efficiency of tobacco cells. Archives of Phytopathology and Plant Protection 50(1-2), 24-32.

Nishikori, T., Naganawa, H., Muraoka, Y., Aoyagi, T., Umezawa, H., 1986. Plispastins; new inhibitors of phospholipase A2 produced by Bacillus cereus BMG302-fF67. ӀӀӀ. Structural elucidation of plispastins. Journal of Atibiotics 39, 755-761.

Ongena, M., Jacques, P., 2008. Bacillus lipopeptides: versatile weapons for plant disease biocontrol. Trends in Microbiology 16(3), 115-125.

Ongena, M., Duby, F., Jourdan, E., Beaudry, T., Jadin, V., Dommes, J., Thonart, P., 2005b. Bacillus subtilis M4 decreases plant susceptibility towards fungal pathogens by increasing host resistance associated with differential gene expression. Applied Microbiology and Biotechnology 67(5), 692-698.

Ongena, M., Jacques, P., Touré, Y., Destain, J., Jabrane, A., Thonart, P., 2005a. Involvement of fengycin-type lipopeptides in the multifaceted biocontrol potential of Bacillus subtilis. Applied Microbiology and Biotechnology 69(1), 29.

Osouli, S., Afsharmanesh, H., 2016. To evaluate the effects of secondary metabolites produced by Bacillus subtilis mutant M419 against Papilio demoleus L. and Aspergillus flavus. Acta Ecologica Sinica 36(6), 492-496.

Patel, H., Tscheka, C., Edwards, K., Karlsson, G., Heerklotz, H., 2011. All-or-none membrane permeabilization by fengycin-type lipopeptides from Bacillus subtilis QST713. Biochimica et Biophysica Acta (BBA)-Biomembranes 1808(8), 2000-2008.

Peypoux, F., Bonmatin, J.M., Wallach, J., 1999. Recent trends in the biochemistry of surfactin. Applied Microbiology and Biotechnology 51(5), 553-563.

Raaijmakers, J.M., De Bruijn, I., Nybroe, O., Ongena, M., 2010. Natural functions of lipopeptides from Bacillus and Pseudomonas: more than surfactants and antibiotics. FEMS Microbiology Reviews 34(6), 1037-1062.

Rahman, M., Nahar, M.A., Sahariar, M.S., Karim, M.R., 2015. Plant growth regulators promote growth and yield of summer tomato (Lycopersicone sculentum Mill.). Progressive Agriculture 26(1), 32-37.

Ramey, B.E., Koutsoudis, M., von Bodman, S.B., Fuqua, C., 2004. Biofilm formation in plant-microbe associations. Current Opinion in Microbiology 7(6), 602-609.

Rivardo, F., Turner, R.J., Allegrone, G., Ceri, H., Martinotti, M.G., 2009. Anti-adhesion activity of two biosurfactants produced by Bacillus spp. prevents biofilm formation of human bacterial pathogens. Applied Microbiology and Biotechnology 83, 541-553.

Romero, D., de Vicente, A., Rakotoaly, R.H., Dufour, S.E., Veening, J.W., Arrebola, E., Cazorla, F.M., Kuipers, O.P., Paquot, M., Pérez-García, A., 2007. The iturin and fengycin families of lipopeptides are key factors in antagonism of Bacillus subtilis toward Podosphaera fusca. Molecular Plant-Microbe Interactions 20(4), 430-440.

Rosenberg, E., Ron, E.Z., 1999. High-and low-molecular-mass microbial surfactants. Applied Microbiology and Biotechnology 52(2), 154-162.

Sotoyama, K., Akutsu, K., Nakajima, M., 2016. Biological control of Fusarium wilt by Bacillus amyloliquefaciens IUMC7 isolated from mushroom compost. Journal of General Plant Pathology 82(2), 105-109.

Souto, G.I., Correa, O.S., Montecchia, M.S., Kerber, N.L., Pucheu, N.L., Bachur, M., Garcia, A.F., 2004. Genetic and functional characterization of a Bacillus sp. strain excreting surfactin and antifungal metabolites partially identified as iturin‐like compounds. Journal of Applied Microbiology 97(6), 1247-1256.

Stein, T., 2005. Bacillus subtilis antibiotics: structures, syntheses and specific functions. Molecular Microbiology 56(4), 845-857.

Steller, S., Sokoll, A., Wilde, C., Bernhard, F., Franke, P., Vater, J., 2004. Initiation of surfactin biosynthesis and the role of the SrfD-thioesterase protein. Biochemistry 43(35), 11331-11343.

Sun, L., Lu, Z., Bie, X., Lu, F., Yang, S., 2006. Isolation and characterization of a co-producer of fengycins and surfactins, endophytic Bacillus amyloliquefaciens ES-2, from Scutellaria baicalensis Georgi. World Journal of Microbiology and Biotechnology 22(12), 1259-1266.

Tang, J.S., Gao, H., Hong, K., Yu, Y., Jiang, M.M., Lin, H.P., Ye, W.C., Yao, X.S., 2007. Complete assignments of 1H and 13C NMR spectral data of nine surfactin isomers. Magnetic Resonance in Chemistry 45(9), 792-796.

Tenover, F.C., 2006. Mechanisms of antimicrobial resistance in bacteria. The American Journal of Medicine 119(6), S3-S10.

Tran, H., Ficke, A., Asiimwe, T., Höfte, M., Raaijmakers, J.M., 2007. Role of the cyclic lipopeptide massetolide A in biological control of Phytophthora infestans and in colonization of tomato plants by Pseudomonas fluorescens. New Phytologist 175(4), 731-742.

Tsuge, K., Akiyama, T., Shoda, M., 2001. Cloning, sequencing, and characterization of the iturin A operon. Journal of Bacteriology 183(21), 6265-6273.

Umezawa, H., Aoyagi, T., Nishikiori, T., Okuyama, A., Yamagishi, Y., Hamada, M., Takeuchi, T., 1986. Plipastatins: new inhibitors of phospholipase A2, produced by Bacillus cereus BMG302-fF67. I. Taxonomy, production, isolation and preliminary characterization. The Journal of Antibiotics 39(6), 737-744.

van Loon, L.C., Rep, M., Pieterse, C.M., 2006. Significance of inducible defense-related proteins in infected plants. Annual Review of Phytopathology 44, 135-162.

Van Wees, S.C., Van der Ent, S., Pieterse, C.M., 2008. Plant immune responses triggered by beneficial microbes. Current Opinion in Plant Biology 11(4), 443-448.

Volpon, L., Besson, F., Lancelin, J. M., 1999. NMR structure of active and inactive forms of the sterol‐dependent antifungal antibiotic bacillomycin L. European Journal of Biochemistry 264(1), 200-210.

Zhao, P., Quan, C., Wang, Y., Wang, J., Fan, S., 2014. Bacillus amyloliquefaciens Q‐426 as a potential biocontrol agent against Fusarium oxysporum f. sp. spinaciae. Journal of Basic Microbiology 54(5), 448-456.

Zou, A., Liu, J., Garamus, V.M., Yang, Y., Willumeit, R., Mu, B., 2010. Micellization activity of the natural lipopeptide [Glu1, Asp5] Surfactin-C15 in aqueous solution. The Journal of Physical Chemistry B, 114(8), 2712-271.



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