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Abstract
Microbial biological control agents (MBCAs) are applied to crops for biological control of plant pathogens where they act via a range of modes of action. Some MBCAs interact with plants by inducing resistance or priming plants without any direct interaction with the targeted pathogen. Other MBCAs act via nutrient competition or other mechanisms modulating the growth conditions for the pathogen. Antagonists acting through hyperparasitism and antibiosis are directly interfering with the pathogen. Such interactions are highly regulated cascades of metabolic events, often combining different modes of action. Compounds involved such as signaling compounds, enzymes and other interfering metabolites are produced in situ at low concentrations during interaction. The potential of microorganisms to produce such a compound in vitro does not necessarily correlate with their in situ antagonism. Understanding the mode of action of MBCAs is essential to achieve optimum disease control. Also understanding the mode of action is important to be able to characterize possible risks for humans or the environment and risks for resistance development against the MBCA. Preferences for certain modes of action for an envisaged application of a MBCA also have impact on the screening methods used to select new microbials. Screening of MBCAs in bioassays on plants or plant tissues has the advantage that MBCAs with multiple modes of action and their combinations potentially can be detected whereas simplified assays on nutrient media strongly bias the selection toward in vitro production of antimicrobial metabolites which may not be responsible for in situ antagonism. Risks assessments for MBCAs are relevant if they contain antimicrobial metabolites at effective concentration in the product. However, in most cases antimicrobial metabolites are produced by antagonists directly on the spot where the targeted organism is harmful. Such ubiquitous metabolites involved in natural, complex, highly regulated interactions between microbial cells and/or plants are not relevant for risk assessments. Currently, risks of microbial metabolites involved in antagonistic modes of action are often assessed similar to assessments of single molecule fungicides. The nature of the mode of action of antagonists requires a rethinking of data requirements for the registration of MBCAs.
Highlights
Microbial biological control agents use a great variety of mechanisms to protect plants from pathogens
Important modes of action strengthen the resistance of the plant, e.g., induced resistance or priming, or modulate the local growth conditions for pathogen development, e.g., nutrient competition, but do not interfere directly with the pathogen
3. Current European Union (EU) regulations on registration of microbial biological control agent (MBCA) should allow a science-based differentiation between the majority of compounds involved in modes of action to be considered as safe and not relevant for detailed risk assessment and the limited number of cases relevant for risk assessments where secondary metabolites are present as active ingredients in MBCAs formulations at high concentrations
Summary
Biological control of plant diseases is the suppression of populations of plant pathogens by living organisms (Heimpel and Mills, 2017). Microbial biological control agents protect crops from damage by diseases via different modes of action (Figure 1) They may induce resistance or prime enhanced resistance against infections by a pathogen in plant tissues without direct antagonistic interaction with the pathogen (Pieterse et al, 2014; Conrath et al, 2015). The typical pathways of plants induced by MAMPs resulting in ISR have been studied in details and FIGURE 1 | Microbial biological control agent (MBCA) temporally interacting in situ with the targeted pathogen activating different modes of action in cascades of events. The MBCA induces defense reactions of the plant through a broad variety of signaling compounds which are low molecular weight compounds, in some cases breakdown products of cell walls They are commonly produced by microorganisms at very low millimolar to subnanomolar concentrations for chemical communication between microorganisms and with plants. Common for all necrotrophic pathogens during their saprophytic stage is that they depend on exogenous nutrients available in TABLE 1 | Modes of action in relation to development and use of microbial biological control agents
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