Natural products against fungal growth.
Aflatoxins are the most potent naturally occurring toxin and liver carcinogens known and their contamination of food is a significant risk factor for human health. Conventional chemical and physical approaches have been insufficient to eliminate aflatoxins from food, and the application of synthetic compounds can give rise to notable drug resistance and serious environmental and health problems. Awareness of these problems has led to an urgent need to identify safer alternative strategies. There are various natural compounds that influence aflatoxin contamination of food in different ways, including by inhibiting the growth of aflatoxigenic fungi, blocking aflatoxin biosynthesis, and removing or degrading aflatoxins. These inhibitors, many of which have shown great potentials for the control of aflatoxin contamination, have great promise for the development of new approaches to combatting aflatoxin contamination, and are capable of replacing or complementing conventional strategies. While more and more natural inhibitors are being identified, the modes of action of most of these are poorly understood. Further studies are necessary to better understand the mechanism of action of these compounds before their widespread commercial use. The objective of this chapter is to present the results of studies of the control of aflatoxin contamination using natural products.
- natural products
Aflatoxins are a group of toxic secondary metabolites synthesized by fungi of the
Aflatoxins were first identified in 1960 in England as the cause of the Turkey X disease . There are four major aflatoxins produced in nature: B1, B2, G1, and G2. They are named based on their fluorescence under ultraviolet light, and their relative mobility in thin‐layer chromatography on silica gel. Most
Aflatoxins are the most potent naturally occurring toxins and liver carcinogens known, and their contamination of food is a significant risk factor for human health, particularly in developing countries that lack detection, monitoring, and regulating measures to safeguard the food supply. It has been reported that approximately 4.5 billion people living in developing countries are chronically exposed to uncontrolled amounts of aflatoxins . Long‐term low‐dose dietary exposure to aflatoxins is also a major risk for hepatocellular carcinoma. Aflatoxins have been designated as human liver carcinogens by the International Agency for Research on Cancer . Therefore, the control and elimination of aflatoxigenic fungi and aflatoxins in food have great significance. To minimize potential exposure to aflatoxins, maximum levels of aflatoxins have been established by different countries . The U.S. Food and Drug Administration specified a maximum of 20 ppb total aflatoxins for interstate trading of food and feedstuffs and 0.5 ppb aflatoxin M1 in milk. The European Commission has set the limits on cereals and derived products at 4 ppb for total aflatoxins and 2 ppb for aflatoxin B1, and for nuts and dried fruits subject to further processing at 10 ppb for total aflatoxins and 5 ppb for aflatoxin B1. The Korea Ministry of Food and Drug Safety imposed limits for aflatoxin B1 of 10 ppb and total aflatoxins of 15 ppb.
Chemical and physical approaches are widely used to minimize the risk of aflatoxin contamination of food. These are usually focused on inhibiting the development of spores and mycelia, and/or inactivation of aflatoxins by their transformation to nontoxic compounds. The most common methods include the use of synthetic fungicides, X‐radiation, dehulling or cooking processes, and control of environmental factors during harvest and storage [10, 11]. These strategies are usually expensive, time‐consuming, and inefficient. Some of them also cause major changes in the physical properties of food and a serious loss of nutritive value and therefore are inappropriate to eliminate aflatoxins from food . Synthetic chemicals are still the most widely used recourse to prevent fungal contamination of food crops. However, there are strict regulations on chemical compound use in food, and there is political pressure to remove hazardous chemicals from the market . In addition to these limitations, the application of synthetic fungicides can also give rise to notable drug resistance and serious environmental and health problems . Awareness of these problems has led to an urgent need to identify safer alternative strategies.
Natural products are chemical compounds or substances produced by a living organism, and their use as biocontrol agents provides an opportunity to avoid synthetic fungicides. Over the years, efforts have been made to identify new antifungal materials from natural sources for controlling aflatoxin contamination of food . Many bacteria, fungi, and plants that share ecological niches with and encounter aflatoxigenic fungi have the ability to synthesize compounds that inhibit aflatoxin synthesis or remove aflatoxins from food without significant losses in nutritive value; they therefore could be used to replace or complement conventional strategies. Basically, there are three possible ways of using natural products to avoid the harmful effects of aflatoxin contamination of food and feed: (1) prevent and control aflatoxigenic fungus contamination (fungal growth inhibition), (2) inhibit aflatoxin biosynthesis (aflatoxin production inhibition), and (3) decontamination of aflatoxin‐containing food and feed (aflatoxin detoxification). These microbial metabolites and plant constituents are natural products and therefore are desirable for use in food because they can be easily degraded in nature. A variety of naturally derived compounds have been studied for their antifungal and antiaflatoxigenic activities, many of which have shown great potential for controlling aflatoxin contamination. The objective of this chapter is to present the results of studies of the control of aflatoxin contamination using natural products from bacteria, fungi, and plants.
2. Fungal growth inhibition
|Target of action||Antifungal product||Source||Activity against||Reference|
|Conidia production and/or germination|||
|(E)‐Anethole, p‐anisaldehyde, carvacrol, (−)‐carvone, 1,8‐cineole, (+)‐limonene, myrcene, (±)‐α‐phellandrene, (±)‐α‐pinene||Plants|||
|Membrane formation and/or integrity||Brefeldin A|||
|Clove essential oil|||
|Eugenol, methyl eugenol||Plants|||
|Cell organelles function||Cruentaren|||
The use of bacteria is a promising solution to alleviate fungal contamination in food. In recent years, the study and application of antifungal bacteria has received strong interest. Significant progress has been reported on the isolation and characterization of antifungal compounds. Various bacterial compounds including organic acids, phenyllactic acids, reuterin, and cyclic dipeptides, proteinaceous compounds, and fatty acids have been reported to be able to inhibit the growth of aflatoxigenic fungi (Table 2).
|Strain||Activity against||Inhibitory compound||Target of action||Reference|
|Bacillomycin D||Conidial germination|||
|Iturin A||Cell surface hydrophobicity|||
|Iturin‐like compound||Conidial germination|||
|Monorden, monocillin IV, cerebrosides||Unknown|||
|Heat‐stable low‐molecular weight compounds||Unknown|||
Many bacteria produce organic acids such as lactic, acetic, and propionic acids. The production of these weak organic acids results in an acidic environment that generally restricts the growth of both bacteria and fungi . Phenyllactic acid has been widely reported to have antifungal activities, and its broad‐spectrum antibacterial and antifungal action makes it one of the most extensively studied antifungal organic acids derived from bacteria. Over the last decade, a number of studies have identified phenyllactic acid as the causative agent of antifungal activity. Its lack of toxicity to both animals and humans body, and its lack of any smell make phenyllactic acid a potential candidate for the control of food spoilage . In addition, phenyllactic acid can also play a synergistic role with other metabolites [61, 62]. Reuterin is another antifungal compound produced by bacteria. This low‐molecular‐weight compound has also been reported to possess broad‐spectrum antimicrobial activity. It has been demonstrated to be capable of inhibiting the growth of a wide range of molds including
Fungal metabolites have also been used to reduce aflatoxin contamination in various crops. A recent study showed that culture filtrates of
Plants lack an immune system and must depend on other mechanisms to defend themselves against fungal invaders. One such mechanism is the synthesis of bioactive compounds that act specifically to inhibit fungal growth. Many plant extracts, particularly essential oils, have been reported to possess significant antifungal activity. An extract of
Antifungal peptides and proteins have also been found in insects. Cecropins, originally isolated from the immune hemolymph of the
3. Aflatoxin production inhibition
One important side effect of fungal growth inhibition is the rapid spread of resistant strains. Therefore, inhibitors of aflatoxin production may be a better choice for control and prevention of aflatoxin contamination of food. Current methods to control aflatoxin contamination are mainly based on chemical strategies (pesticides and fungicides). However, the excessive use of chemical treatments has many undesirable consequences: (1) marked pollution of the environment, (2) an increase in resistant pathogen populations, and (3) the presence of chemical residues in food. Specific microbial metabolites and plant constituents have been shown to be effective inhibitors of aflatoxin production without significantly affecting fungal growth; in fact, numerous compounds and extracts possessing inhibitory activity for aflatoxin biosynthesis have been reported. However, tools and techniques have only recently become available to investigate the molecular mechanisms by which these inhibitors regulate aflatoxin biosynthesis .
Microbially derived inhibitors of aflatoxin production are of practical use because of their strong activity and the possibility of large‐scale production. For example, a number of
Plant‐derived inhibitors of aflatoxin production have great potential because not only are they highly effective but also the genes responsible for their biosynthesis could be transferred into susceptible host plants to create transgenic plants that resist aflatoxin contamination by
In principle, there are three possible ways to inhibit aflatoxin biosynthesis (Figure 1). First, there can be alteration of the physiological environment or disturbance of the signaling inputs perceived by the fungus. For example, eugenol is a major phenolic component of essential oils extracted from cloves, cinnamon, and nutmeg. It has been shown in multiple experiments to inhibit aflatoxin biosynthesis. Evidence suggests that eugenol inhibits aflatoxin biosynthesis by lowering the physiological requirement for the enzymes activities involved in responding to oxidative stress. Eugenol treatment of fungi growing on Potato Dextrose Agar plates has been shown to result in the reduction of enzyme activities (glutathione peroxidase, microsomal reductases, superoxide dismutase, and xanthine oxidase) involved in responding to oxidative stress, concomitant with the inhibition of aflatoxin production by up to 50% . Zingerone is another plant‐derived aflatoxin inhibitor isolated from certain parts of
The second way to inhibit aflatoxin biosynthesis is to interfere with the signal transduction networks or gene expression regulation of aflatoxin biosynthesis by, for example, using calmodulin inhibitors, most of which are alkaloid and peptide compounds that have been isolated from a wide variety of natural sources, including many plant species . Multiple lines of evidence support the idea that calcium‐dependent signaling plays an important role in the regulation of aflatoxin biosynthesis . Calmodulin‐binding domains have been identified in the primary sequences of aflatoxin pathway transcriptional regulators (AflR and AflJ) and biosynthetic enzymes, presenting the possibility that calmodulin may influence transcriptional regulation of the aflatoxin biosynthesis gene cluster . Aflastatin A and blasticidin A are well‐known microbial‐derived aflatoxin inhibitors. They are structurally related compounds produced by
The third way to inhibit aflatoxin biosynthesis is to block the activity of aflatoxin biosynthesis‐related enzymes. For example, coumarins have been found to strongly inhibit aflatoxin production without causing significant reductions in fungal growth . It has been suggested that structural similarities between these coumarone and aflatoxins may result in competitive inhibition of biosynthetic enzymes. Terpenoids are a major class of natural products synthesized in plants through the mevalonic acid pathway. There are reports that different terpenoids, including camphene, α‐carotene, limonene, lutein, and zeaxanthin, are inhibitory to aflatoxin biosynthesis in solid or liquid media . The inhibition by terpenoids may occur at the level of whole‐pathway regulation. For example, α‐carotene was found to be able to block the synthesis of norsolorinic acid, the first stable aflatoxin precursor, thereby preventing the accumulation of subsequent pathway intermediates. Caffeine is another well‐studied inhibitor of aflatoxin production, with studies showing that decaffeinated coffee beans and powder support higher aflatoxin production than normal beans and powder, and that incorporation of coffee into growth medium at concentrations of 1% (w/v) inhibits total aflatoxin production by 25%, with no significant reduction in fungal growth. The inhibitory effect of caffeine on glucose uptake is considered to be the possible mode of action for its antiaflatoxigenic activity . Hydroxamic acids, such as 6‐methoxy‐benzoxazolin‐2‐one (MBOA), are also strong inhibitors of aflatoxin biosynthesis. MBOA significantly inhibits α‐amylase induction . It was suggested that the perturbation of sugar utilization by MBOA might be the major reason for its antiaflatoxigenic activity.
4. Aflatoxin detoxification
Aflatoxins are extremely stable under most conditions encountered during food storage, handling, and processing. Therefore, preventing contamination with aflatoxigenic fungi is the most rational and economic approach for controlling aflatoxin contamination of food. However, detoxification of aflatoxin is required for food already contaminated with aflatoxin. Although various methods have been described for detoxification of aflatoxins in foods, the most commonly used physical and chemical approaches are usually high cost or complex processes, and many also result in nutrient loss and food safety issues.
Biological detoxification of aflatoxins by employing natural products has been shown to be very effective in removing aflatoxin from food. In principle, there are four possible biological approaches to avoid the toxic effects of aflatoxins on the human body: (1) remove aflatoxins through surface adsorption to bacterial or fungal cells; (2) transform aflatoxins into nontoxic compounds by enzymatic degradation; (3) introduce aflatoxin adsorbents into contaminated food and feed to bind the toxins and inhibit their absorption from the gastrointestinal tract; and (4) metabolize aflatoxin into relatively nontoxic compounds via different metabolic pathways (Figure 2).
Aflatoxin detoxifying microorganisms were first demonstrated in 1996, when Ciegler et al. identified a
Over the last few decades, considerable literature has accumulated that describes methods for removing aflatoxins using different microorganisms. Pure cultures of bacteria and fungi that detoxify aflatoxins, which include
Many reports state that the use of brewer’s yeast cells as an animal feed additive resulted in a reduction in the toxic effects of aflatoxins . In an early study, some yeast strains isolated from West African maize were found to be able to bind 15–60% (w/w) of aflatoxin B1 and this toxin binding was highly strain specific . Yeast cells of
The use of LAB in food fermentation dates back several centuries. Early studies showed that different LABs, including
Enzymatic inactivation of aflatoxins is another attractive strategy for food decontamination. Several microorganisms can transform aflatoxin B1 to aflatoxicol and other less toxic or nontoxic compounds. It has been reported that aflatoxin B1 can be detoxified into aflatoxin B2a during yoghurt fermentation ; that aflatoxin B1 is detoxified during fermentation of milk by lactic bacteria ; and that
Mycotoxin‐producing fungi are also able to degrade or transform aflatoxins and possibly use them as a source of energy under suitable conditions. Several investigators have observed that aflatoxigenic strains produce large amounts of aflatoxins that usually decrease during continued incubation of the cultures .
Another practical approach to reducing the toxicity of aflatoxin to humans and animals is the addition of non‐nutritional inert adsorbents to the diet. These adsorbents sequester the aflatoxins in the gastrointestinal tract, thereby minimizing their toxic effects. Various adsorbents have been tested, including activated carbon, bentonite, cholestyramine, hydrated sodium calcium aluminosilicate, and zeolite, and produced promising results with respect to aflatoxin binding . However, their application in food is limited because of their negative impacts such as reducing nutrient utilization. Therefore, the use of microorganisms and other natural products has become increasingly attractive as a reliable alternative to chemical adsorbents in the gastrointestinal tract.
The potential application of natural products as aflatoxin binders in human foods and animal feeds depends on their stability and the residence time of the complex in the gastrointestinal tract. The adhesion of aflatoxin‐binding microorganisms to intestinal cells appears to be highly strain specific. Yeast cells generally show very low adhesion to the intestine but are capable of withstanding the harsh environment of the gastrointestinal tract . Animal feeding experiments have shown that the addition of whole cells or cell walls of
LAB cells usually show considerably higher adhesion to intestinal cells compared with that of yeast cells. However, it has been reported that aflatoxin binding considerably reduced the adhesive properties of some LAB strains and resulted in the faster excretion of immobilized aflatoxin B1 . Gratz et al. also found that pre‐exposure of the cells of a
Aflatoxins absorbed into the bodies of humans or animals may also be metabolized into relatively nontoxic compounds via different metabolic pathways. The process of detoxification of aflatoxins usually involves removing the double bond of the terminal furan ring or opening the lactone ring. Once the lactone ring is opened, further reactions can occur to alter their binding properties to DNA and proteins . The main reactions of aflatoxin metabolism in humans and animals are hydroxylation, oxidation, and demethylation. There are numerous studies concerning the metabolism of aflatoxin
5. Application of natural inhibitors
The preferred strategy for reducing the concentrations of aflatoxins in foods is prevention of aflatoxin formation during preharvest and postharvest of the various susceptible crops. In this context, non‐aflatoxigenic
To achieve effective control of aflatoxin contamination in food, high concentrations of natural compounds are generally needed. The incorporation of natural compounds into packaging materials can be a useful strategy to solve this problem. In the last decade, there have been plentiful studies of the development of active packaging materials. Because the introduction of protective agents in packaging materials can be used to protect food without direct addition of new chemicals, it has received great interest from both the food industry and academic communities. Many natural extracts, such as essential oils and their constituents, are categorized as flavorings in Europe and are categorized as Generally Recognized as Safe (GRAS) by the U.S. Food and Drug Administration. For this reason, they have often been proposed for and used in active packaging. For the purpose of the design of active packaging, it is necessary to establish which compounds have antiaflatoxigenic properties and what concentration is required to obtain maximum inhibition. In addition, because the volatile nature of some components, the release rate of the encapsulated compounds from their polymer matrix should be controlled, thereby magnifying their antiaflatoxigenic action on the product by both direct contact and through the head space of the packaging. The processes of encapsulating natural aflatoxin inhibitors into the polymer matrix should also be carefully controlled. Previous studies have shown notable losses of the active compounds during the film formation step of the casting technique .
Nanotechnology‐based systems associated with natural compounds are also a good option. There are many well‐known benefits of associating natural compounds with nanotechnological drug‐delivery systems . One good example is a nanoemulsion: in an emulsified form, natural compounds may be applied as an aqueous‐based treatment. In fact, fine droplets may improve the delivery of inhibitory compounds to cereals because they may be able to penetrate into the cracks and crevices on the cereal surfaces. Nanoemulsions are emulsion droplets with a radius below 100 nm, which can be formed using both high‐energy and low‐energy methods . High‐energy methods require specialized mechanical devices, such as high pressure valve homogenizers, sonicators and microfluidizers. These devices are capable of generating intense mechanical forces that can intermingle and disrupt the oil and water phases. Low‐energy methods rely on the spontaneous formation of nano‐sized oil droplets, which is a physicochemical process that occurs under appropriate conditions with certain combinations of surfactant, oil, and water. The spontaneous emulsification method has recently been reported to be suitable for application in the food industry for fabricating effective antimicrobial nanoemulsions from essential oils .
As mentioned previously, genetic engineering is another way to utilize these compounds. Host crop species can be engineered to gain resistance to aflatoxin contamination by incorporation of the genes for biosynthesis of natural inhibitors. There are likely hundreds, if not thousands, of natural compounds that influence aflatoxin biosynthesis at concentrations ranging from submicromolar to millimolar. Unfortunately, many of these inhibitors are not suitable for genetic engineering. The complexity of altering plant natural product pathways makes it difficult to engineer crop species resistant to aflatoxin contamination. In addition, the majority of aflatoxin inhibitors reported so far were tested
In summary, there are various natural compounds that influence aflatoxin contamination in food through different ways, including inhibition of the growth of aflatoxigenic fungi, blocking aflatoxin biosynthesis, and removal or degradation of aflatoxin. These inhibitors are highly promising for the development of new approaches to fighting aflatoxin contamination in food and have the capability to replace or complement conventional strategies. A common feature of many inhibitors is their antioxidant activity; yet, the relationship of antiaflatoxigenic activity and antioxidant activity is unknown. Some inhibitors of aflatoxin production are specifically targeted to the biosynthesis of aflatoxin without affecting the development of the fungal cells. However, most inhibitors also inhibit fungal growth at higher concentrations. This may indicate that secondary metabolism (aflatoxin) is sensitive to stress resulting from low concentrations of growth‐inhibitory compounds. The production of norsolorinic acid, the first stable intermediate in the aflatoxin biosynthetic pathway, was inhibited in parallel with aflatoxin production at the regulatory level of biosynthesis rather than at specific steps within the pathway, indicating the importance of this intermediate. More and more natural inhibitors are being identified, yet the modes of action of most are poorly understood. Further studies are necessary to better understand the mechanisms of action of those compounds before they can be widely used commercially. Using new biological approaches, researchers are now combining datasets from profiling of transcripts, proteins, and metabolites generated using inhibitory compounds with different modes of action, which will provide useful information for dissecting different facets of aflatoxin regulation.
Gourama H, Bullerman LB. Aspergillus flavusand Aspergillus parasiticus: Aflatoxigenic fungi of concern in foods and feeds: A review. Journal of Food Protection. 1995; 58(12):1395-1404.
Klich MA. Soil fungi of some low‐altitude desert cotton fields and ability of their extracts to inhibit Aspergillus flavus. Mycopathologia. 1998; 142:97-100.
Bennett JW, Leong PM, Kruger S, Keyes D. Sclerotial and low aflatoxigenic morphological variants from haploid and diploid Aspergillus parasiticus. Cellular and Molecular Life Sciences. 1986; 42(7):848-851.
Perrone G, Susca A, Cozzi G, Ehrlich K, Varga J, Frisvad JC, Samson RA. Biodiversity of Aspergillus species in some important agricultural products. Studies in Mycology. 2007; 59:53-66.
Robens J, Cardwell K. The costs of mycotoxin management to the USA: Management of aflatoxins in the United States. Journal of Toxicology: Toxin Reviews. 2003; 22(2-3):139-152.
Allcroft R, Carnaghan RBA, Sargeant K, O’kelly J. A toxic factor in Brazilian groundnut meal. Veterinary Record. 1961; 73:428-429.
Van Egmond HP. Current situation on regulations for mycotoxins. Overview of tolerances and status of standard methods of sampling and analysis. Food Additives & Contaminants. 1989; 6(2):139-188.
Wogan GN. Aflatoxins as risk factors for hepatocellular carcinoma in humans. Cancer Research. 1992; 52(7 Supplement):2114s–2118s.
Van Egmond HP, Schothorst RC, Jonker MA. Regulations relating to mycotoxins in food. Analytical and Bioanalytical Chemistry. 2007; 389(1):147-157.
Bata Á, Lásztity R. Detoxification of mycotoxin‐contaminated food and feed by microorganisms. Trends in Food Science & Technology. 1999; 10(6):223-228.
Piva G, Galvano F, Pietri A, Piva A. Detoxification methods of aflatoxins. A review. Nutrition Research. 1995; 15(5):767-776.
Line JE, Brackett RE. Factors affecting aflatoxin B1 removal by Flavobacterium aurantiacum. Journal of Food Protection. 1995; 58(1):91-94.
Pal KK, Gardener BM. Biological control of plant pathogens. The Plant Health Instructor. 2006; 2:1117-1142.
White TC, Marr KA, Bowden RA. Clinical, cellular, and molecular factors that contribute to antifungal drug resistance. Clinical Microbiology Reviews. 1998; 11(2):382-402.
Klich MA. Environmental and developmental factors influencing aflatoxin production by Aspergillus flavusand Aspergillus parasiticus. Mycoscience. 2007; 48(2):71-80.
Rana BK, Singh UP, Taneja V. Antifungal activity and kinetics of inhibition by essential oil isolated from leaves of Aegle marmelos. Journal of Ethnopharmacology. 1997; 57(1):29-34.
Hamilton‐Kemp TR, McCracken CT, Loughrin JH, Andersen RA, Hildebrand DF. Effects of some natural volatile compounds on the pathogenic fungi Alternaria alternataand Botrytis cinerea. Journal of Chemical Ecology. 1992; 18(7):1083-1091.
Caccioni DR, Guizzardi M. Inhibition of germination and growth of fruit and vegetable postharvest pathogenic fungi by essential oil components. Journal of Essential Oil Research. 1994; 6(2):173-179.
Wilson CL, Franklin JD, Otto BE. Fruit volatiles inhibitory to Monilinia fructicolaand Botrytis cinerea. Plant Disease. 1987; 71(4):316-319.
El Ghaouth A, Arul J, Grenier J, Asselin A. Antifungal activity of chitosan on two postharvest pathogens of strawberry fruits. Phytopathology. 1992; 82(4):398-402.
Altomare C, Perrone G, Stornelli C, Bottalico A. Quaderni della Scuola di specializzazione in Viticoltura ed Enologia. University of Torino, Italy. 1998; 22:59-66.
Chitarra GS, Abee T, Rombouts FM, Posthumus MA, Dijksterhuis J. Germination of Penicillium paneumconidia is regulated by 1‐octen‐3‐ol, a volatile self‐inhibitor. Applied and Environmental Microbiology. 2004; 70(5):2823-2829.
Rosengaus RB, Lefebvre ML,Traniello JF. Inhibition of fungal spore germination by Nasutitermes: evidence for a possible antiseptic role of soldier defensive secretions. Journal of Chemical Ecology. 2000; 26(1):21-39.
Cole L, Davies D, Hyde GJ, Ashford AE. Brefeldin A affects growth, endoplasmic reticulum, golgi bodies, tubular vacuole system, and secretory pathway in Pisolithus tinctorius. Fungal Genetics and Biology. 2000; 29(2):95-106.
Ahmad A, Khan A, Akhtar F, Yousuf S, Xess I, Khan LA, Manzoor N. Fungicidal activity of thymol and carvacrol by disrupting ergosterol biosynthesis and membrane integrity against Candida. European Journal of Clinical Microbiology & Infectious Diseases. 2011; 30(1):41-50.
Pinto E, Vale‐Silva L, Cavaleiro C, Salgueiro L. Antifungal activity of the clove essential oil from Syzygium aromaticum on Candida, Aspergillus and dermatophyte species. Journal of Medical Microbiology. 2009; 58(11):1454-1462.
Thevissen K, Terras FR, Broekaert WF. Permeabilization of fungal membranes by plant defensins inhibits fungal growth. Applied and Environmental Microbiology. 1999; 65(12): 5451-5545.
Ahmad A, Khan A, Manzoor N, Khan LA. Evolution of ergosterol biosynthesis inhibitors as fungicidal against Candida. Microbial Pathogenesis. 2010; 48(1):35-41.
Bard M, Albrecht MR, Gupta N, Guynn CJ, Stillwell W. Geraniol interferes with membrane functions in strains of Candida and Saccharomyces. Lipids. 1988; 23(6):534-538.
Khan A, Ahmad A, Akhtar F, Yousuf S, Xess I, Khan LA, Manzoor N. Ocimum sanctumessential oil and its active principles exert their antifungal activity by disrupting ergosterol biosynthesis and membrane integrity. Research in Microbiology. 2010; 161(10):816-823.
Abad LR, D’Urzo MP, Liu D, Narasimhan ML, Reuveni M, Zhu JK, Niu X, Singh NK, Hasegawa PM, Bressan RA. Antifungal activity of tobacco osmotin has specificity and involves plasma membrane permeabilization. Plant Science. 1996; 118(1):11-23.
de Lira Mota KS, de Oliveira Pereira F, de Oliveira WA, Lima IO, de Oliveira Lima E. Antifungal activity of Thymus vulgarisL. essential oil and its constituent phytochemicals against Rhizopus oryzae: interaction with ergosterol. Molecules. 2012; 17(12):14418-14433.
Roberts WK, Selitrennikoff CP. Zeamatin, an antifungal protein from maize with membrane‐permeabilizing activity. Microbiology. 1990; 136(9):1771-1778.
Kunze B, Steinmetz H, Höfle G, Huss M, Wieczorek H, Reichenbach H. Cruentaren, a new antifungal salicylate‐type macrolide from Byssovorax cruenta(Myxobacteria) with inhibitory effect on mitochondrial ATPase activity. Journal of Antibiotics. 2006; 59(10):664.
Aerts AM, Bammens L, Govaert G, Carmona‐Gutierrez D, Madeo F, Cammue B, Thevissen K. The antifungal plant defensin HsAFP1 from Heuchera sanguineainduces apoptosis in Candida albicans. Frontiers in Microbiology. 2011; 2:47.
Tian J, Ban X, Zeng H, He J, Chen Y, Wang Y. The mechanism of antifungal action of essential oil from dill ( Anethum graveolensL.) on Aspergillus flavus. PLoS One. 2012; 7(1):e30147.
Fudou R, Iizuka T, Yamanaka S. Haliangicin, a novel antifungal metabolite produced by a marine myxobacterium. 1. Fermentation and biological characteristics. The Journal of Antibiotics. 2001; 54(2):149-152.
Jeandet P, Douillet‐Breuil AC, Bessis R, Debord S, Sbaghi M, Adrian M. Phytoalexins from the Vitaceae: biosynthesis, phytoalexin gene expression in transgenic plants, antifungal activity, and metabolism. Journal of Agricultural and Food Chemistry. 2002; 50(10):2731-2741.
Wu XZ, Cheng AX, Sun LM, Sun SJ, Lou HX. Plagiochin E, an antifungal bis (bibenzyl), exerts its antifungal activity through mitochondrial dysfunction‐induced reactive oxygen species accumulation in Candida albicans. Biochimica et Biophysica Acta (BBA)‐General Subjects. 2009; 1790(8):770-777.
El‐Banna N, Winkelmann G. Pyrrolnitrin from Burkholderia cepacia: antibiotic activity against fungi and novel activities against streptomycetes. Journal of Applied Microbiology. 1998; 85(1):69-78.
Romagnoli C, Bruni R, Andreotti E, Rai MK, Vicentini CB, Mares D. Chemical characterization and antifungal activity of essential oil of capitula from wild Indian Tagetes patulaL. Protoplasma. 2005; 225(1-2):57-65.
Ueki M, Taniguchi M. The mode of action of UK‐2A and UK‐3A, novel antifungal antibiotics from Streptomyces sp. 517‐02. The Journal of Antibiotics. 1997; 50(12):1052-1057.
Khan A, Rahman M, Islam MS. Antibacterial, antifungal and cytotoxic activities of amblyone isolated from Amorphophallus campanulatus. Indian Journal of Pharmacology. 2008; 40(1):41.
Moyne AL, Shelby R, Cleveland TE, Tuzun S. Bacillomycin D: an iturin with antifungal activity against Aspergillus flavus. Journal of Applied Microbiology. 2001; 90(4):622-629.
Munimbazi C, Bullerman LB. Inhibition of aflatoxin production of Aspergillus parasiticusNRRL 2999 by Bacillus pumilus. Mycopathologia. 1997; 140(3):163-169.
Cho SJ, Lee SK, Cha BJ, Kim YH, Shin KS. Detection and characterization of the Gloeosporium gloeosporioidesgrowth inhibitory compound iturin A from Bacillus subtilisstrain KS03. FEMS Microbiology Letters. 2003; 223(1):47-51.
Chitarra GS, Breeuwer P, Nout MJR, Van Aelst AC, Rombouts FM, Abee T. An antifungal compound produced by Bacillus subtilisYM 10-20 inhibits germination of Penicillium roqueforticonidiospores. Journal of Applied Microbiology. 2003; 94(2):159-166.
Wicklow DT, Joshi BK, Gamble WR, Gloer JB, Dowd PF. Antifungal metabolites (monorden, monocillin IV, and cerebrosides) from Humicola fuscoatra Traaen NRRL 22980, a mycoparasite of Aspergillus flavussclerotia. Applied and Environmental Microbiology. 1998; 64(11):4482-4484.
Gourama H, Bullerman LB. Antimycotic and antiaflatoxigenic effect of lactic acid bacteria: a review. Journal of Food Protection. 1995; 58(11):1275-1280.
Coallier‐Ascah J, Idziak ES. Interaction between Streptococcus lactis and Aspergillus flavuson production of aflatoxin. Applied and Environmental Microbiology. 1985; 49(1): 163-167.
Gourama H, Bullerman LB. Inhibition of growth and aflatoxin production of Aspergillus flavusby Lactobacillus species. Journal of Food Protection. 1995; 58(11):1249-1256.
Gourama H, Bullerman LB. Anti‐aflatoxigenic activity of Lactobacillus caseipseudoplantarum. International Journal of Food Microbiology. 1997; 34(2):131-143.
Batish VK, Grover S, Lal R. Screening lactic starter cultures for antifungal activity. Cultured Dairy Products Journal. 1989; 24:23-25.
Roy U, Batish VK, Grover S, Neelakantan S. Production of antifungal substance by Lactococcus lactissubsp. lactis CHD‐28.3. International Journal of Food Microbiology. 1996; 32(1-2):27-34.
Wanga SL, Yieh TC, Shih L. Purification and characterization of a new antifungal compound produced by Pseudomonas aeruginosaK‐187 in a shrimp and crab shell powder medium. Enzyme and Microbial Technology. 1999; 25(3):439-446.
Dhanasekaran D, Thajuddin N, Panneerselvam A. An antifungal compound: 4′ phenyl‐1‐napthyl–phenyl acetamide from Streptomyces sp. DPTB16. Facta Universitatis Ser Med Biol. 2008; 15:7-12.
Ono M, Sakuda S, Suzuki A, Isogai A. Aflastatin A, a novel inhibitor of aflatoxin production by aflatoxigenic fungi. The Journal of Antibiotics. 1997; 50(2):111-118.
Narayana KJ, Prabhakar P, Vijayalakshmi MUVVA, Venkateswarlu Y, Krishna PS. Study on bioactive compounds from Streptomyces sp. ANU 6277. Polish Journal of Microbiol-ogy. 2008; 57(1):35.
Ross RP, Morgan S, Hill C. Preservation and fermentation: past, present and future. International Journal of Food Microbiology. 2002; 79(1):3-16.
Lavermicocca P, Valerio F, Visconti A. Antifungal activity of phenyllactic acid against molds isolated from bakery products. Applied and Environmental Microbiology. 2003; 69(1):634-640.
Rizzello C, Cassone A, Coda R, Gobbetti M. Antifungal activity of sourdough ferment-ed wheat germ used as an ingredient for bread making. Food Chemistry. 2011; 127(3):952-959.
Ryan LA, Zannini E, Dal Bello F, Pawlowska A, Koehler P, Arendt EK. Lactobacillus amylovorusDSM 19280 as a novel food‐grade antifungal agent for bakery products. International Journal of Food Microbiology. 2011; 146(3):276-283.
Axelsson LT, Chung TC, Dobrogosz WJ, Lindgren SE. Production of a broad spectrum antimicrobial substance by Lactobacillus reuteri. Microbial Ecology in Health and Disease. 1989; 2(2):131-136.
Ndagano D, Lamoureux T, Dortu C, Vandermoten S, Thonart P. Antifungal activity of 2 lactic acid bacteria of the Weissella genus isolated from food. Journal of Food Science. 2011; 76(6):305-311.
Garofalo C, Zannini E, Aquilanti L, Silvestri G, Fierro O, Picariello G, Clementi F. Selection of sourdough lactobacilli with antifungal activity for use as biopreservatives in bakery products. Journal of Agricultural and Food Chemistry. 2012; 60(31):7719-7728.
Reddy KRN, Reddy CS, Muralidharan K. Potential of botanicals and biocontrol agents on growth and aflatoxin production by Aspergillus flavusinfecting rice grains. Food Control. 2009; 20(2):173-178.
Nakaya K, Omata K, Okahashi I, Nakamura Y, Kolkenbrock H, Ulbrich N. Amino acid sequence and disulfide bridges of an antifungal protein isolated from Aspergillus giganteus. The FEBS Journal. 1990; 193(1):31-38.
García-Olmedo F, Molina A, Alamillo JM, Rodríguez-Palenzuéla P. Plant defense peptides. Peptide Science. 1998; 47(6):479-491.
Lee DG, Shin SY, Maeng CY, Jin ZZ, Kim KL, Hahm KS. Isolation and characterization of a novel antifungal peptide from Aspergillus niger. Biochemical and Biophysical Research Communications. 1999; 263(3):646-651.
Bhatnagar D. The inhibitory effect of neem ( Azadirachta indica) leaf extracts on aflatoxin synthesis in Aspergillus parasiticus. Journal of the American Oil Chemists’ Society. 1988; 65(7):1166-1168.
Bhargava KS, Dixit SN, Dubey NK, Tripathi RD. Fungitoxic properties of Ocimum canum. Journal of Indian Botanical Society. 1981; 60:24-27.
Huang Z, White DG, Payne GA. Corn seed proteins inhibitory to Aspergillus flavusand aflatoxin biosynthesis. Phytopathology. 1997; 87(6):622-627.
Chen ZY, Brown RL, Russin JS, Lax AR, Cleveland TE. A corn trypsin inhibitor with antifungal activity inhibits Aspergillus flavusα‐amylase. Phytopathology. 1999; 89(10):902-907.
Gooday GW. Biosynthesis of the fungal wall‐mechanisms and implications the first Fleming Lecture. Microbiology. 1977; 99(1):1-11.
Bell AA. Biochemical mechanisms of disease resistance. Annual Reviews of Plant Physiol-ogy. 1981; 32:21-81.
Roberts WK, Selitrennikoff CP. Isolation and partial characterization of two antifungal proteins from barley. Biochimica et Biophysica Acta (BBA)‐General Subjects. 1986; 880(2-3):161-170.
Boller T, Gehri A, Mauch F, Vögeli U. Chitinase in bean leaves: induction by ethylene, purification, properties, and possible function. Planta. 1983; 157(1):22-31.
Mauch F, Mauch‐Mani B, Boller T. Antifungal hydrolases in pea tissue. 11. Inhibition of fungal growth by combinations of chitinase and p‐1,3‐glucanase. Plant Physiology. 1988; 88(3):936-942.
Roberts WK, Selitrennikoff CP. Plant and bacterial chitinases differ in antifungal activity. Journal of General Microbiology. 1988; 134(1):169-176.
Lockey TD, Ourth DD. Formation of pores in Escherichia colicell membranes by a cecropin isolated from hemolymph of Heliothis virescenslarvae. European Journal of Biochemistry. 1996; 236(1):263-271.
Powell WA, Catranis CM, Maynard CA. Synthetic antimicrobial peptide design. MPMI‐Molecular Plant Microbe Interactions. 1995; 8(5):792.
Holmes RA, Boston RS, Payne GA. Diverse inhibitors of aflatoxin biosynthesis. Applied Microbiology and Biotechnology. 2008; 78(4):559-572.
Wasser SP, Weis AL. Medicinal properties of substances occurring in higher basidiomycetes mushrooms: current perspectives (review). International Journal of medicinal mushrooms. 1999; 1(1):31-62.
Slameňová D, Lábaj J, Kogan G, Šandula J, Bresgen N, Eckl P. Protective effects of fungal (1→ 3)‐β‐D‐glucan derivatives against oxidative DNA lesions in V79 hamster lung cells. Cancer Letters. 2003; 198(2):153-160.
Yuan C, Mei Z, Shangxi L, Yi L. PSK protects macrophages from lipoperoxide accumulation and foam cell formation caused by oxidatively modified low‐density lipoprotein. Atherosclerosis. 1996; 124(2):171-181.
Guo FC, Kwakkel RP, Williams BA, Li WK, Li HS, Luo JY, Li XP, Wei YX, Yan ZT, Verstegen MWA. Effects of mushroom and herb polysaccharides, as alternatives for an antibiotic, on growth performance of broilers. British Poultry Science. 2004; 45(5):684-694.
Xu Y. Perspectives on the 21st century development of functional foods: bridging Chinese medicated diet and functional foods. International Journal of Food Science & Technology. 2001; 36(3):229-242.
Jermnak U, Yoshinari T, Sugiyama Y, Tsuyuki R, Nagasawa H, Sakuda S. Isolation of methyl syringate as a specific aflatoxin production inhibitor from the essential oil of Betula alba and aflatoxin production inhibitory activities of its related compounds. International Journal of Food Microbiology. 2012; 153(3):339-344.
Mahmoud AL. Antifungal action and antiaflatoxigenic properties of some essential oil constituents. Letters in Applied Microbiology. 1994; 19(2):110-113.
Sidhu OP, Chandra H, Behl HM. Occurrence of aflatoxins in mahua ( Madhuca indicaGmel.) seeds: Synergistic effect of plant extracts on inhibition of Aspergillus flavusgrowth and aflatoxin production. Food and Chemical Toxicology. 2009; 47(4):774-777.
Jayashree T, Subramanyam C. Antiaflatoxigenic activity of eugenol is due to inhibition of lipid peroxidation. Letters in Applied Microbiology. 1999; 28(3):179-183.
Kim JH, Campbell BC, Mahoney NE, Chan KL, Molyneux RJ. Identification of phenolics for control of Aspergillus flavususing Saccharomyces cerevisiaein a model target‐gene bioassay. Journal of Agricultural and Food Chemistry. 2004; 52(26):7814-7821.
DeLucca AJ, Palmgren MS, Daigle DJ. Depression of aflatoxin production by flavonoid‐type compounds from peanut shells. Phytopathology. 1987; 77(11):1560-1563.
De Luca C, Passi S, Fabbri AA, Fanelli C. Ergosterol oxidation may be considered a signal for fungal growth and aflatoxin production in Aspergillus parasiticus. Food Additives & Contaminants. 1995; 12(3):445-450.
Song DK, Karr AL. Soybean phytoalexin, glyceollin, prevents accumulation of aflatoxin B 1 in cultures of Aspergillus flavus. Journal of Chemical Ecology. 1993; 19(6):1183-1194.
Gonçalez E, Felicio JD, Pinto MM. Biflavonoids inhibit the production of aflatoxin by Aspergillus flavus. Brazilian Journal of Medical and Biological Research. 2001; 34(11):1453-1456.
Paster N, Juven BJ, Harshemesh H. Antimicrobial activity and inhibition of aflatoxin B1 formation by olive plant tissue constituents. Journal of Applied Bacteriology. 1988; 64(4):293-297.
Jayashree T, Subramanyam C. Oxidative stress as a prerequisite for aflatoxin production by Aspergillus parasiticus. Free Radical Biology and Medicine. 2000; 29(10):981-985.
Lee SE, Mahoney NE, Campbell BC. Inhibition of aflatoxin B1 biosynthesis by piperlongumine isolated from Piper longumL. Journal of Microbiology and Biotechnology. 2002; 12(4):679-682.
Ehrlich K, Ciegler A. Effect of phytate on aflatoxin formation by Aspergillus parasiticusand Aspergillus flavusin synthetic media. Mycopathologia. 1984; 87(1-2):99-103.
Graf E, Empson KL, Eaton, JW. Phytic acid. A natural antioxidant. Journal of Biological Chemistry. 1987; 262(24):11647-11650.
Martínez‐Luis S, Pérez‐Vásquez A, Mata R. Natural products with calmodulin inhibitor properties. Phytochemistry. 2007; 68(14):1882-1903.
Praveen Rao, J, Subramanyam C. Calmodulin mediated activation of acetyl-CoA carboxylase during aflatoxin production by Aspergillus parasiticus. Letters in Applied Microbiology. 2000; 30(4):277-281.
Juvvadi PR, Chivukula S. Putative calmodulin‐binding domains in aflatoxin biosynthesis–regulatory proteins. Current Microbiology. 2006; 52(6):493-496.
Kondo T, Sakurada M, Okamoto S, Ono M, Tsukigi H, Suzuki A, Sakuda S. Effects of aflastatin A, an inhibitor of aflatoxin production, on aflatoxin biosynthetic pathway and glucose metabolism in Aspergillus parasiticus. The Journal of Antibiotics. 2001; 54(8):650-657.
Yoshinari T, Akiyama T, Nakamura K, Kondo T, Takahashi Y, Muraoka Y, Nonomura Y, Nagasawa H, Sakuda, S. Dioctatin A is a strong inhibitor of aflatoxin production by Aspergillus parasiticus. Microbiology. 2007; 153(8):2774-2780.
Yoshinari T, Noda Y, Yoda K, Sezaki H, Nagasawa H, Sakuda S. Inhibitory activity of blasticidin A, a strong aflatoxin production inhibitor, on protein synthesis of yeast: Selective inhibition of aflatoxin production by protein synthesis inhibitors. The Journal of Antibiotics. 2010; 63(6):309-314.
Mabrouk SS, El‐Shayeb NMA. Inhibition of aflatoxin production in Aspergillus flavusby natural coumarone and chromones. World Journal of Microbiology and Biotechnology. 1992; 8(1):60-62.
Roze LV, Beaudry RM, Keller NP, Linz JE. Regulation of aflatoxin synthesis by FadA/cAMP/protein kinase A signaling in Aspergillus parasiticus. Mycopathologia. 2004; 158(2):219-232.
Brodhagen M, Keller NP. Signalling pathways connecting mycotoxin production and sporulation. Molecular Plant Pathology. 2006; 7(4):285-301.
Vergopoulou S, Galanopoulou D, Markaki P. Methyl jasmonate stimulates aflatoxin B1 biosynthesis by Aspergillus parasiticus. Journal of Agricultural and Food Chemistry. 2001; 49(7):3494-3498.
Burow GB, Nesbitt TC, Dunlap J, Keller NP. Seed lipoxygenase products modulate Aspergillus mycotoxinbiosynthesis. Molecular Plant‐Microbe Interactions. 1997; 10(3): 380-387.
Greene‐McDowelle DM, Ingber B, Wright MS, Zeringue HJ, Bhatnagar D, Cleveland TE. The effects of selected cotton‐leaf volatiles on growth, development and aflatoxin production of Aspergillus parasiticus. Toxicon. 1999; 37(6):883-893.
Buchanan RL, Hoover DG, Jones SB. Caffeine inhibition of aflatoxin production: mode of action. Applied and Environmental Microbiology. 1983; 46(5):1193-1200.
Kato‐Noguchi H, Macías FA. Possible mechanism of inhibition of 6‐methoxy‐benzoxazolin‐2 (3H)‐one on germination of cress ( Lepidium sativumL.). Journal of Chemical Ecology. 2006; 32(5):1101-1109.
Ciegler A, Lillehoj EB, Peterson RE, Hall HH. Microbial detoxification of aflatoxin. Applied Microbiology. 1966; 14(6):934-939.
Lillehoj EB, Ciegler A, Hall, HH. Aflatoxin B1 uptake by Flavobacterium aurantiacumand resulting toxic effects. Journal of Bacteriology. 1967; 93(1):464-471.
Line JE, Brackett RE. Role of toxin concentration and second carbon source in microbial transformation of aflatoxin B1 by Flavobacterium aurantiacum. Journal of Food Protection. 1995; 58(9):1042-1044.
Teniola OD, Addo PA, Brost IM, Färber P, Jany KD, Alberts JF, van Zyl WH, Steyn PS, Holzapfel WH. Degradation of aflatoxin B 1 by cell‐free extracts of Rhodococcus erythropolis and Mycobacterium fluoranthenivoranssp. nov. DSM44556 T. International Journal of Food Microbiology. 2005; 105(2):111-117.
Nout MJR. Effect of Rhizopus and Neurospora spp. on growth of Aspergillus flavusand A. parasiticusand accumulation of aflatoxin B1 in groundnut. Mycological Research. 1989; 93(4):518-523.
Oliveira CAF, Jager AV, Corassin CH, Bovo F, Reddy KR. Recent trends in microbiological decontamination of aflatoxins in foodstuffs. In: INTECH Open Access Publisher. Croatia, Rijeka; 2013.
Nout MJR, Motarjemi Y. Assessment of fermentation as a household technology for improving food safety: A joint FAO/WHO workshop. Food Control. 1997; 8(5-6):221-226.
Santin E, Paulillo AC, Maiorka A, Nakaghi LSO, Macari M, Silva AVF, Alessi AC. Evaluation of the efficacy of Saccharomyces cerevisiaecell wall to ameliorate the toxic effects of aflatoxin in broilers. International Journal of Poultry Science. 2003; 2(5):341-344.
Shetty PH, Jespersen L. Saccharomyces cerevisiaeand lactic acid bacteria as potential mycotoxin decontaminating agents. Trends in Food Science & Technology. 2006; 17(2):48-55.
Çelýk K, Denlý M, Savas T. Reduction of toxic effects of aflatoxin B1 by using baker yeast ( Saccharomyces cerevisiae) in growing broiler chicks diets. Revista Brasileira de Zootecnia. 2003; 32(3):615-619.
Stanley VG, Ojo R, Woldesenbet S, Hutchinson DH, Kubena LF. The use of Saccharo-myces cerevisiaeto suppress the effects of aflatoxicosis in broiler chicks. Poultry science. 1993; 72(10):1867-1872.
Sampaio Baptista A, Horii J, Antonia Calori‐Domingues M, Micotti da Glória E, Mastrodi Salgado J, Roberto Vizioli M. The capacity of manno‐oligosaccharides, thermolysed yeast and active yeast to attenuate aflatoxicosis. World Journal of Microbiology and Biotechnology. 2004; 20(5):475-481.
Devegowda G, Aravind BIR, Morton MG. Saccharomyces cerevisiaeand mannanoligosaccharides to counteract aflatoxicosis in broilers. In: Proceedings of Australian Poultry Science Symposium Sydney. 1996; 103:106.
Karaman M, Basmacioglu H, Ortatatli M, Oguz H. Evaluation of the detoxifying effect of yeast glucomannan on aflatoxicosis in broilers as assessed by gross examination and histopathology. British Poultry Science. 2005; 46(3):394-400.
Thompson ED, Knights BA, Parks LW. Identification and properties of a sterol‐binding polysaccharide isolated from Saccharomyces cerevesiae. Biochimica et Biophysica Acta (BBA)‐General Subjects. 1973; 304(1):132-141.
El‐Nezami H, Kankaanpaa P, Salminen S, Ahokas J. Ability of dairy strains of lactic acid bacteria to bind a common food carcinogen, aflatoxin B 1. Food and Chemical Toxicology. 1998; 36(4):321-326.
Peltonen K, El‐Nezami H, Haskard C, Ahokas J, Salminen, S. Aflatoxin B1 binding by dairy strains of lactic acid bacteria and bifidobacteria. Journal of Dairy Science. 2001; 84(10):2152-2156.
Turbic A, Ahokas JT, Haskard, CA. Selective in vitro binding of dietary mutagens, individually or in combination, by lactic acid bacteria. Food Additives & Contaminants. 2002; 19(2):144-152.
Haskard C, Binnion C, Ahokas J. Factors affecting the sequestration of aflatoxin by Lactobacillus rhamnosusstrain GG. Chemico‐Biological Interactions. 2000; 128(1):39-49.
Lahtinen SJ, Haskard CA, Ouwehandz AC, Salminenz SJ, Ahokasy JT. Binding of aflatoxin B1 to cell wall components of Lactobacillus rhamnosusstrain GG. Food Additives and Contaminants. 2004; 21:158-164.
Haskard CA, El‐Nezami HS, Kankaanpää PE, Salminen S, Ahokas JT. Surface binding of aflatoxin B1 by lactic acid bacteria. Applied and Environmental Microbiology. 2001; 67(7):3086-3091.
Megalla SE, Hafez AH. Detoxification of aflatoxin B1 by acidogenous yoghurt. Mycopathologia. 1982; 77(2):89-91.
Megalla SE, Mohran MA. Fate of a atoxin B‐1 in fermented dairy products. Mycopathologia. 1984; 88:27-29.
Liu DL, Yao DS, Liang R, Ma L, Cheng WQ, Gu LQ. Detoxification of aflatoxin B 1 by enzymes isolated from Armillariella tabescens. Food and Chemical Toxicology. 1998; 36(7):563-574.
Liang ZH, Li JX, He YL, Guan S, Wang N, Ji C, Niu TG. AFB1 bio‐degradation by a new strain‐Stenotrophomonas sp. Agricultural Sciences in China. 2008; 7(12):1433-1437.
Teunisson DJ, Robertson JA. Degradation of pure aflatoxins by Tetrahymena pyriformis. Applied Microbiology. 1967; 15(5):1099-1103.
Detroy RW, Hesseltine CW. Transformation of aflatoxin B1 by steroid‐hydroxylating fungi. Canadian Journal of Microbiology. 1969; 15(6):495-500.
Schultz DL, Luedecke LO. Effect of neutral fats and fatty acids on aflatoxin production. Journal of Food Protection. 1977; 40(5):304-308.
Hamid AB, Smith JE. Degradation of aflatoxin by Aspergillus flavus. Microbiology. 1987; 133(8):2023-2029.
Huwig A, Freimund S, Käppeli O, Dutler H. Mycotoxin detoxication of animal feed by different adsorbents. Toxicology Letters. 2001; 122(2):179-188.
Lewis SJ, Freedman AR. Review article: The use of biotherapeutic agents in the prevention and treatment of gastrointestinal disease. Alimentary Pharmacology & Therapeutics. 1998; 12(9):807-822.
Madrigal‐Santillán E, Madrigal‐Bujaidar E, Márquez‐Márquez R, Reyes A. Antigeno-toxic effect of Saccharomyces cerevisiaeon the damage produced in mice fed with aflatoxin B 1 contaminated corn. Food and Chemical Toxicology. 2006; 44(12):2058-2063.
Diaz DE, Hagler WM, Hopkins BA, Whitlow LW. Aflatoxin binders I: in vitro binding assay for aflatoxin B1 by several potential sequestering agents. Mycopathologia. 2003; 156(3):223-226.
Kankaanpää P, Tuomola E, El‐Nezami H, Ahokas J, Salminen SJ. Binding of aflatoxin B1 alters the adhesion properties of Lactobacillus rhamnosusstrain GG in a Caco‐2 model. Journal of Food Protection. 2000; 63(3):412-414.
Gratz S, Mykkänen H, Ouwehand AC, Juvonen R, Salminen S, El‐Nezami H. Intestinal mucus alters the ability of probiotic bacteria to bind aflatoxin B1 in vitro. Applied and Environmental Microbiology. 2004; 70(10):6306-6308.
El‐Nezami H, Mykkänen H, Kankaanpää P, Salminen S, Ahokas J. Ability of Lactobacillus and Propionibacterium strains to remove aflatoxin B1 from the chicken duodenum. Journal of Food Protection. 2000; 63(4):549-552.
Bolognani F, Rumney CJ, Rowland IR. Influence of carcinogen binding by lactic acid‐producing bacteria on tissue distribution and in vivo mutagenicity of dietary carcinogens. Food and Chemical Toxicology. 1997; 35(6):535-545.
Basappa SC, Shantha T. Methods for detoxification of aflatoxins in foods and feeds: A critical appraisal. Journal of Food Science and Technology. 1996; 33(2):95-107.
Salhab AS, Edwards GS. Comparative in vitro metabolism of aflatoxicol by liver preparations from animals and humans. Cancer Research. 1977; 37(4):1016-1021.
Roebuck BD, Wogan GN. Species comparison of in vitro metabolism of aflatoxin B1. Cancer Research. 1977; 37(6):1649-1656.
Roebuck BD, Siegel WG, Wogan GN. In vitro metabolism of aflatoxin B2 by animal and human liver. Cancer Research. 1978; 38(4):999-1002.
Chipley JR, Mabee MS, Applegate KL, Dreyfuss M.S. Further characterization of tissue distribution and metabolism of [14C] aflatoxin B1 in chickens. Applied Microbiology. 1974; 28(6):1027-1029.
Donnelly PJ, Stewart RK, Ali SL, Conlan AA, Reid KR, Petsikas D, Massey TE. Biotransformation of aflatoxin B1 in human lung. Carcinogenesis. 1996; 17(11):2487-2494.
Yoshizawa H, Uchimaru R, Kamataki T, Kato R, Ueno Y. Metabolism and activation of aflatoxin B1 by reconstituted cytochrome P‐450 system of rat liver. Cancer Research. 1982; 42(3):1120-1124.
Sánchez‐González L, Cháfer M, González‐Martínez C, Chiralt A, Desobry S. Study of the release of limonene present in chitosan films enriched with bergamot oil in food simulants. Journal of Food Engineering. 2011; 105(1):138-143.
Saraf S. Applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010; 81(7):680-689.
McClements DJ, Rao J. Food‐grade nanoemulsions: formulation, fabrication, properties, performance, biological fate, and potential toxicity. Critical Reviews in Food Science and Nutrition. 2011; 51(4):285-330.
Chang Y, McLandsborough L, McClements DJ. Physicochemical properties and antimicrobial efficacy of carvacrol nanoemulsions formed by spontaneous emulsification. Journal of Agricultural and Food Chemistry. 2013; 61(37):8906-8913.
Gurr SJ, Rushton PJ. Engineering plants with increased disease resistance: What are we going to express? Trends in Biotechnology. 2005; 23(6):275-282.