In addition to the economic aspects and infrastructural facilities, the climatic factors characterising an area must be considered for the choice of the crop to be cultivated. At present, this issue is relevant because of climatic changes that affect most areas of the world. Climate change can result in the adoption of different pathogen control strategies and agronomical techniques, owing to the possible adaptation of new pathogens to the new climatic scenario. For example, many areas with a Mediterranean climate that are traditionally free from freezing events either in winter or early spring have recently faced relevant frost damage during such periods, which seriously threatens the economic profit of crops ^[15][16][15,16]. In addition, for other areas such as Central and Eastern Asia, Central–North America, Northern India, Australia, and the Mediterranean Basin, the occurrence of “hot spots” (i.e., temperature > 40 °C for many consecutive days, accompanied by the absence of rainfall) during summer pose a risk to wheat cultivation [17] and can cause severe damage to heat-tolerant crops such as olive [18]. Edaphic (i.e., soil fertility, texture, and porosity) and biotic (i.e., occurrence of bees, pests, and pathogens) factors must also be considered to avoid future problems due to climate change.

In addition to area suitability, the right choice of cultivars is another basic element that can allow the success of the crop according to sustainability criteria. For woody species, the choice is of basic importance and, according to soil characteristics, should also consider the choice of rootstock. The right choice is even more critical, particularly when the crop reaches a new cultivation area [19]. The cultivar choice for herbaceous crops is also important in the context of climate change, as shown by an extensive survey performed in Germany with cereal producers. Farmers judged eco-stability, grain yield performance, and steadiness as being the most important cultivar requirements [20].

The healthy phytosanitary status of seeds, tubers, plantlets, potted plants, and propagative material is a fundamental prerequisite for initiating cultural cycles. At present, this aspect is particularly important considering the extensive global circulation of these commodities. In recent years, the relevant increase in global plant circulation regarding the agricultural and forest trade has dramatically increased the possibility of pests and pathogens to rapidly reach new countries and, consequently, to colonise and infect new crops and the same crops cultivated on another continent [21]. Once introduced in a new area, phytopathogens can become part of the new environment(s) depending on a series of factors, such as the number of introduction events, the transmission rate of the pathogen, the density and spatial variation of the susceptible host, the favourability of the climatic conditions, the synchronicity between host susceptibility, and the pathogen life cycle [22]. An efficient surveillance system at the border should be developed in each country to rapidly intercept new threats before they can be established in a new territory. This issue is particularly important for countries that have not yet developed a phytosanitary regulation system based on quarantine principles. In contrast, seed companies and plant nurseries should efficiently implement all preventive measures that can reduce the colonisation of plant material (i.e., effective pathogen control strategies during plant growth and disinfection of plant material before shipping). In addition, farmers should carefully monitor crops, particularly during the first phases of growth, to observe and eliminate potential diseases.

One of the pillars of the European Common Agricultural Policy (CAP) is the maintenance and enhancement of soil fertility; correct soil management is one of the fundamental prerequisites for sustainability in agriculture [23]. According to agroecological principles, some effective practices can be applied to herbaceous and woody crops to maintain and augment soil fertility. Crop rotation with leguminous species and the planting of cover crops between tree rows are methods that can ensure, over a long-term period, the maintenance of natural soil fertility ^[24][25][24,25]. Crop rotation can also result in a better control of some soil-borne diseases, such as in potatoes affected by Rhizoctonia solani and Streptomyces scabies [26]. In addition, the application of plant growth-promoting rhizobacteria (PGPR), biofertilisers, composts, mycorrhiza, biochars, and humic and fulvic acids can augment nutrient acquisition and assimilation, improve soil texture and plant growth, and induce systemic resistance to biotic and abiotic stresses ^{[26][27][28][29][30][31][32]}[26,27,28,29,30,31,32]. For example, the distribution to the soil of a biofertiliser that contained a mixed fungal and bacterial microflora induced conferred protection against Fusarium wilt of banana caused by Fusarium oxysporum f. sp. cubense after three years [33]. Paecilomyces variotii, a fungus obtained from agro-industrial compost, showed efficacy in the control of Fusarium wilt of melon caused by Fusarium oxysporum f. sp. melonis [34]. However, care should be given to the correct choice of compounds released into the soil to increase their overall fertility. In some circumstances, organic matter, particularly animal manure, can release antibiotics that can perturb native microflora, causing adverse effects on the crop [35]. It should be noted that balanced crop nutrition is an essential component of any integrative program for crop protection [36].

Given that the application of compounds for crop protection aims to deposit the highest amount of the active ingredient on the target plant part (i.e., buds, leaves, and canopy) in which the pathogen resides, an effective and desirable reduction of the spread of any compound in the environment can be achieved by the appropriate calibration of the sprayers. At present, it is possible to adjust the sprayer nozzles to achieve the intended target (i.e., the plant part that shows symptoms of disease), which also reduces water utilisation [37]. Soil solarisation is a well-known technique that, when properly applied, can effectively control important soil-borne pathogens. However, the utilisation of plastic covers poses a relevant concern for their subsequent removal and disposal [38]. Organic farming largely benefits from such preventive measures to obtain effective pathogen control, particularly soilborne pathogens [39].

3. Sustainable Agriculture and Pathogen Control

3.1. The Basis for an Effective Sustainable Pathogen Control

Knowledge of the genomic structure, virulence factors, and epidemiology of pathogens is the basis for developing fine-tuned strategies for the effective control of biotic diseases in crops. Selected biocontrol agents or compounds with potential curative effects should be tested against different strains of pathogens that represent the entire population structure. In addition, the disease cycle of the target pathogen should be fully understood to precisely apply the biocontrol agent/compound before and during plant colonisation or the internal multiplication of the microorganism. Some examples of the basic studies that link crop and pathogen epidemiology to the selection of biocontrol agents and fine-tune the spread of active ingredients for disease control are as follows ^{[40][41][42][43][44][45][46]}[40,41,42,43,44,45,46]. Knowledge of the pathogen cycle of diseases is also the basis for the development and implementation of disease forecasting ^[47][48][47,48]. Moreover, the sustainability of modern pathogen control should be considered in addition to crop productivity, the ecological function of the crop, and the social acceptance of the strategy [49]. A report that concerns either the effectiveness or the social impact of different strategies to control fire blight of apple, caused by Erwinia amylovora, in Switzerland has been prepared. A thorough investigation performed by interviewing experts and a literature data search revealed that biological control performed with Aureobasidium pullulans is either effective or widely accepted in rural areas because of its feasibility, durability, low impact on animals, biodiversity, soil and water habitation, low cost, and acceptance by consumers [50]. In this case, the majority of the inhabitants of an area are aware of the importance and efficacy of sustainable agriculture for the maintenance and improvement of their lifestyle and environmental safety.

3.2. Current Control Strategies

Integrated pest management (IPM) is the current strategy that allows for the effective control of many plant pathogens in many cases. According to the European Union Framework Directive on the sustainable use of pesticides (Directive 2009/128/EC), IPM “means careful consideration of all available plant protection methods and subsequent integration of appropriate measures that discourage the development of populations of harmful organisms and keep the use of plant protection products and other forms of intervention to levels that are economically and ecologically justified and reduce or minimise risks to human health and the environment. IPM emphasises the growth of a healthy crop with the least possible disruption to agro-ecosystems and encourages natural pest control mechanisms”. In addition, the FAO IPM programme involves three large areas located in Asia, the Near East, and West Africa to improve farming skills, raise the awareness of smallholder farmers of the risks posed by traditional agrochemicals, and promote sustainable agriculture (https://www.fao.org/agriculture/crops/core-themes/theme/pests/ipm/en/, accessed on 22 May 2022). However, given the diversity and complexity of agricultural scenarios, IPM can differ significantly among countries, and each crop of a definite area of cultivation should apply the IPM criteria according to the local reality and a holistic approach; thus, the combination of control tactics into a planned strategy can provide more effective and sustainable results than the single-tactic approach ^[51][52][51,52]. The development and utilisation of ad hoc web-based platforms illustrating control thresholds, cultural practices that can influence disease attack, pathogen virulence, and fungicide efficacy can help farmers, advisors, and researchers to better plan the control strategy according to a real-time assessment of the environmental conditions of the area [53]. The application of the IPM strategy on a large scale would benefit from ad hoc studies that provide updated information on the current control strategies applied to any crop in an area in order to identify the lack of knowledge in the field, to be resolved through future studies. These systematic maps of knowledge have proven useful in applying IPM to arable crops (i.e., wheat, barley, oat, potato, sugar beet, and oilseed rape) cultivated in large areas in Sweden [54]. A refined IPM strategy which combines all the validated methods for monitoring and reducing the impact of the diseases would allow researchers to control apple scab and apple powdery mildew, caused by Venturia inaequalis and Podosphaera leucotricha, respectively. This strategy includes disease monitoring and forecasting, ecofriendly fungicides, adequate orchard sanitation, biological control, and insect control through mating disruption. It is comparable with the results obtained by conventional pest management methods [55]. IPM is also the basis for a transition from a chemical to a biological control strategy in Canada regarding greenhouse vegetable crops [56]. In addition, IPM strategies largely benefit from the cultivation of resistant/tolerant cultivars, as observed for the more effective application of biocontrol agents such as Bacillus mycoides to a sugar beet cultivar that is more tolerant to Cercospora beticola, or Bacillus subtilis towards chickpeas infected by Fusarium oxysporum f. sp. ciceris [57]. In the Netherlands and Ireland, the utilisation of novel potato cultivars resistant to late blight, caused by Phytophthora infestans, in combination with real-time pathogen population monitoring and checking of its genetic structure allowed for a reduction of 80–90% of fungicide use (https://www.wur.nl/en/newsarticle/more-sustainable-potato-production-through-extended-ipm-for-late-blight.htm, accessed on 22 May 2022). The protection of crops starting from the seed is another relevant option for better management of diseases. Trichoderma gamsii, applied to maize kernels, has been proven effective in reducing pink ear rot caused by Fusarium verticillioides and root infection [58]. Despite the higher incidence of pathogens in the crop, the application of organic farming principles for some years can also support, in many circumstances, the effective biological control of pathogens [59]. The observed increase in ecological intensifications of the agro-ecosystem promotes a higher occurrence of beneficial microorganisms in the crop [59]. The synergism between IPM strategies and organic farming principles in relation to pathogen control could provide benefits for improving environmental quality, farm economic viability, and soil and human health [60]. At present, the success of IPM and organic farming in relation to pathogen control is based on three research sectors that are closely related to each other: disease forecasting models, biological control, and environmentally friendly natural products or compounds.

3.2.1. Disease-Forecasting Models

Disease forecasting is based on mechanical models designed with the input of climatic data and the pathogen cycle of disease to alert the grower on whether, when, and how to apply an agrochemical or a biocontrol agent to protect crops. Such models are dynamic because they analyse the changes in the components of an epidemic over time according to external variables (i.e., climatic data, pathogen multiplication, and plant growth stage in relation to disease development) [47]. An effective example of a forecasting model that allows a relevant reduction in pesticide distribution in the environment is vite.net^® [61]. Based on a decision support system that calculates vineyard parameters (i.e., air, soil, plant, pathogen, and disease development) and a web-based tool that analyses such data, vite.net^® provides information for Plasmopara viticola management in the vineyard. The system is flexible and can be tailored to a single vineyard or an area characterised by high similarity. This tool was largely utilised by grape growers on more than 17,000 h in 2017 in Italy, Spain, Portugal, Greece, Romania, and the United Kingdom and allowed for a reduction of approximately 50% in pesticide utilisation ^[47][61][47,61]. Another effective and used disease-forecasting model is Brassica_spot^TM that is applied to manage Albugo candida, a causal agent of white blister of Brassica crops (i.e., radish and broccoli) in Australia [62]. The application of the model allowed for a reduction of more than 80% of the disease and reduced the number of pesticide sprays from fourteen to one or two per year. In addition, the introduction of a resistant cultivar and the simple change in the time of irrigation from 2000 h to 4000 h also decreased disease incidence [62]. Similarly, in Florida, the Strawberry Advisory System (SAS) based on local weather data allows growers to reduce the use of chemical sprays for controlling anthracnose, caused by Colletotrichum spp., and grey mould, caused by Botrytis cinerea [63], by 50%. In South Korea, the EPIRICE model was developed to assess the daily risk for the occurrence of rice blast caused by Magnaporthe oryzae [48]. The model utilises some climatic data linked to fungus multiplication, such as air relative humidity, temperature, and precipitation, and can be used to predict the risk of disease at an early stage [48].

3.2.2. Biological Control

Biological control agents for plant diseases are defined as naturally occurring microorganisms capable of suppressing the growth and proliferation of a target pathogen by different mechanisms of action (i.e., competition for space and nutrients, antibiosis, predation, induced host resistance, and lytic enzymes). In addition to living microorganisms, they sometimes utilise metabolite(s) that can be sprayed directly onto crops [64]. Beneficial microorganisms are registered as plant protection products, and they are usually applied to crops at a high density once or several times during the growing season. In the United States and Canada, government agencies are responsible for confirming the biosafety of the biocontrol agents (i.e., the Environmental Protection Agency (EPA) in the United States, and the Pest Management Regulatory Agency (ARLA) in Canada). In Europe, according to Regulation 1107/2009 for plant protection products, the authorisation for commercialising biocontrol agents is obtained through some related steps: (a) the bioactive microorganism should be approved at the European level by the European Food Safety Authority (EFSA) according to the physiochemical properties of the substance, its risk profile for human health, and its risk profile for the environment; (b) formulated products should be authorised at the member state level; (c) further scrutiny with regard to organic agriculture requirements. In addition, the Directorate General for Health and Food Safety (DG SANTE), the Standing Committee on Plants, Animal, Food, and Feed (PAFF Committee), and the Rapporteur Member State are involved in the decision according to Directive 91/414, which states that any active substance should be included in an approved EU list (Annex 1), and its further application must be authorised by member states. These procedures take a long time, thus creating an overall slowness for final approval [65]. The causal agents of plant diseases can have either a worldwide occurrence in specific crops or local distribution. For the first case, the application of the Nagoya protocol of October 2014, for the “Access and the Fair and Equitable Benefit-sharing of Genetic Resources” that restricts the international exchange of biological material, can result in a limitation on the circulation and use of biological control agents that are selected in a different geographical area [66]. Consequently, given the increase in organic food demand and the current Green Deal policy, the selection of native local biocontrol agents is of paramount importance [11]. It should be noted that this selection largely depends on the specific pathosystem under study. Two approaches illustrate how it is possible to proceed: (a) selection through consecutive screenings for testing the effectiveness of the biocontrol agent (i.e., in vitro assays for antibiosis, lytic enzymes, and antimicrobial metabolites, in planta assays for colonisation, control performance, and induced resistance); (b) selection through the assistance of genetic/genomic studies (i.e., the use of genetic markers for finding single biocontrol traits, genome-wide DNA markers for selecting complex traits) ^[11][67][11,67]. The durability of biocontrol agents is another important prerequisite for their long-standing efficacy. Indeed, there are documented reports of a significant reduction in the control effectiveness of Botrytis cinerea in Astilbe hybrids, as shown by Pseudomonas chlororaphis after eight treatments [68]. In some circumstances, natural selection yields biocontrol agents that are capable of displaying long-term positive effects on some diseases, such as for soybean root rot caused by Fusarium spp., Pythium spp., and Rhizoctonia solani in Northeast China. In this case, a naturally occurring suppressive soil was analysed, and Trichoderma harzianum, Pochonia clamydosporia, Paecilomyces lilacinus, and Pseudomonas fluorescens strains have been found to inhibit the fungal pathogens of soybean roots [69]. Another well-known example is the natural occurrence of mycoviruses of the family Hypoviridae, which infect Cryphonectria parasitica, the causal agent of chestnut blight. Upon infection, the virus incites hypovirulence in the fungus by reducing its parasitic growth and sporulation capacity. The virus can be isolated from chestnut cankers and utilised as a biocontrol agent to cure trees by inhibiting further canker development. In addition, the virus is capable of spreading naturally in the forest and reaching other infected trees [70]. Fungi, bacteria, and yeast are the most widely used biocontrol agents. The following species are among the most versatile: Trichoderma harzianum, Trichoderma viride, Bacillus subtilis, and Pseudomonas fluorescens. All of them, indeed, have shown control activity towards some common fungal pathogens such as Botrytis cinerea, Monilinia fructicola, Plasmopara viticola, Puccinia graminis, and Erisiphe spp. [71]. Rhizobium (Agrobacterium) radiobacter strain K84 is among the most known biocontrol agents used for many years to control crown gall caused by Agrobacterium tumefaciens [72]. A stand-alone effective biocontrol agent has been also selected for apple scab caused by Venturia inaequalis, namely Cladosporium cladosporioides H39, that, over a wide range of environment, showed a high control level and appears effective even when applied after some days from the infection event [73]. Similarly, Bacillus amyloliquefaciens strains are capable of effectively controlling Fusarium equiseti in broad bean cultivation [74]. In some circumstances, a single biocontrol agent is capable of effectively reducing two diseases caused by distantly related microorganisms, as was seen for Paecilomyces variotii, which showed control activity towards both the bacterium Xanthomonas vesicatoria, the causal agent of bacterial spot of tomato, and Fusarium oxysporum f. sp. melonis, the causal agent of Fusarium wilt of melon [34]. Trichoderma spp. are among the most studied biocontrol agents in agriculture. Through different metabolic pathways, the induction of systemic resistance to the plant, multiple adaptive mechanisms, antimicrobial molecules, and antagonistic behaviour, Trichoderma strains can either promote plant growth or act as effective biocontrol agents against fungal species under numerous agricultural conditions, including in greenhouses and nurseries ^[75][76][75,76]. These strains account for the greatest proportion of fungal biocontrol agents against the phytopathogenic microorganisms investigated, and many commercial formulations that contain a single Trichoderma strain or a mixture of different Trichoderma strains are available ^[75][77][75,77]. A series of common and widespread phytopathogenic fungi, such as Rhizoctonia solani, Fusarium oxysporum, Botrytis cinerea, Pythium spp., Sclerotinia spp., Verticillium spp., Phytophthora spp., and Alternaria spp. can be controlled by generalist Trichoderma spp. strains ^[75][78][75,78]. Other fungal genera that also show antagonistic activity toward phytopathogenic fungi are Alternaria, Aspergillus, Penicillium, Pichia, Candida, Talaromyces, and nonpathogenic Fusarium, Pythium, and Verticillium [79]. Pichia anomala is effective in controlling postharvest crown rot of banana caused by Colletotrichum musae, Fusarium verticillioides, and Lasidiodiplodia theobromae [80]. In addition, Ampelomyces quisqualis is commercially available for the preventive control of powdery mildew fungi in different crops, such as eggplant, cucumber, tomato, and strawberry. Pseudomonad strains provide a very large amount of potential biocontrol agents that can be found within the following species and species complexes: Pseudomonas fluorescens, P. chlororaphis, P. putida, P. syringae, P. aureofaciens, P. protegens, P. mandelii, P. corrugata, P. koreensis, and P. gessardii [81]. However, very few commercially available products are currently available: P. fluorescens for Erwinia amylovora; nonpathogenic Pseudomonas syringae for postharvest disease of fruits, potato, and sweet potato; Pseudomonas chlororaphis for fungal diseases of ornamental crops and turf grass; Pseudomonas aureofaciens for lawn and grass management against soil-borne fungi. Genetic instability and poor shelf life are among the main causes of the limited registration of pseudomonads as biocontrol agents [81]. Bacillus species have a higher shelf life due to their possibility to form endospores, and have many potential biocontrol agents, stemming from their ample antagonism mechanisms (i.e., antibiosis, enzymes, lipopeptides, competition for space, and nutrients), are also present in this genus, with Bacillus subtilis, B. amyloliquefaciens, and B. polymixa being the richest in providing biocontrol effectiveness [82].