Acknowledgements

use of synthetic pesticides, there are several concerns regarding the biological and environmental stability of BCAs. For example, the population of A. flavus including atoxigenic strains is highly diverse. This entails that there is a risk under certain environmental conditions that atoxigenic strains outcross with toxigenic A. flavus and thereafter produce mycotoxins [26, 62]. In addition, it is not guaranteed whether the atoxigenic strains can survive for a long time and

Care should be taken that besides successful control of plant pathogens, and BCAs themselves do not produce toxic substances. For instance, C. rosea secretes gliotoxin which is toxic metabolite to human. Also, it was reported that some Trichoderma strains harbor trichothecenes (Tri) genes that translate into proteins similar to Fusarium Tri proteins [179, 180]. This entails that Trichoderma spp. share the production of trichothecenes toxins (such as T-2 toxin) with Fusarium spp. In addition, gliotoxin and viridian produced by T. harzianum, T. viride and T. virens showed their phytotoxic effect by reducing seed germination rate in wheat and human toxicity [28]. Therefore, spreading such a microorganism into the environment may impose an extra burden to food safety and public health. Additionally, from the economical point of view, it is necessary to estimate the total cost of application and the need for seasonal reapplication of the BCAs, so

Controlling mycotoxins is an important aspect in the management of mycotoxigenic pathogens, which adds an extra challenge to find an effective biocontrol agent to control the fungal growth and toxin production simultaneously. It is very well known that one fungal pathogen can produce simultaneously several unrelated mycotoxins, as an example F. graminearum produces DON and ZEN which both have two different biosynthetic pathways. The scientific research has mostly been focusing to control one type of mycotoxin. Consequently, it will be more valuable to select a single biocontrol agent able to simultaneously suppress the production of both toxins. It is crucial that the selected BCAs are tolerant to mycotoxins [169] which

Some mycotoxins can be modified by the plant through alteration of their chemical structure "i.e. conjugation to a glucose moiety and hence called plant metabolites of mycotoxins or modified or masked mycotoxins" [181]. For example, DON is transformed to deoxynivalenol-3-glucoside (DON3G) in the plant as a part of the plant defense mechanism. These masked forms of mycotoxins can be hydrolyzed back into their parent forms "DON" inside human and animal body. Therefore, it is of paramount importance to take into account the effect of biocontrol agents on the production of (masked) mycotoxins and to deeply investigate whether the efficacy of the selected BCAs is due to an actual reduction of mycotoxin content based on a direct inhibition of their production by the pathogen or due to enhancing the plant immunity which may increase the plant ability to form more DON3G as in this case the total mycotoxin content in the plant will remain unchanged. Furthermore, the underlying mechanism between the parent mycotoxin, host and BCAs remains obscure and should be further investigated. In addition, other categories of mycotoxins, however they pose health risks, are underexplored such as enniatins, emerging mycotoxins produced by Fusarium spp., [14, 182] have not been tested with BCAs and this necessitates the need for further investigation.

Different BCAs with different modes of action, formulation, treatments, application time were tested showing that it may be difficult to have a single BCA able to diminish all the regulated

what is the short term and long term effect on the soil microenvironment.

it does not exceed costs of current practices.

74 Mycotoxins - Impact and Management Strategies

will guarantee the long term efficiency in the field.

This work was supported by the EU project Horizon 2020-MYCOKEY "Integrated and innovative key actions for mycotoxin management in the food".
