Introduction

COVID-19, more than a pandemic, has been considered a syndemic or an infectious disease that interacts with biological, social and behavioral factors. In this way, understanding the effect of SARS-CoV-2 (^{Martín-Moreno et al., 2021}), the virus that causes the disease, clinically or epidemiologically, would require the interaction with non-transmissible chronic diseases, comorbidities, malnutrition, pollution, demography, urbanism, etc., which are a product, in many cases, of socioeconomic inequalities (^{Horton, 2020}), but also of human recklessness. In 2020, during the first and second pandemic cycles, an attempt was perceived to acknowledge the backwardness of government health systems, even in developed nations, as well as the importance of reducing socioeconomic inequalities and strengthening preventive medicine (^{González-Salgado et al., 2021}; ^{Martín-Moreno et al., 2021}). The World Health Organization (WHO) itself was criticized for its slow responses and the bureaucratization of its international management processes. Currently, at the end of this edition, mitigation efforts seem to center on the classic clinical approaches and the promotion of extensive and global vaccination programs with a strong preeminence of the pharmaceutical industry, therefore prevention, as a systemic health model, seems reduced to economic interests (Editor´s note).

However, farming activities in Mexico, from a Phytopathological point of view, propose the confrontation of COVID-19 and subsequent pandemics in a better way. One feasible vision is the use of microorganisms that benefit plants, to improve the efficiency of fertilizers, pest and disease management, and other crop stress factors. The use of microorganisms may help reduce the application of agrochemicals and increase tolerance to abiotic and biotic stress, which would increase the yield and the quality of agricultural products, reducing direct costs related to production and the environment. This approach would translate into better food for the human population, which could improve its response to non-infectious, infectious and degenerative diseases as a result of a strengthened immune system, as well as a higher quality of life, in general. The aim of this revision is to describe a sustainable approach to our agriculture, in which natural biological mechanisms gradually integrate into contemporary agriculture. We therefore suggest reinforcing the links between the sectors related to agriculture and defining priority research topics. This could help improve our pest and disease management systems, water use, pertinence of fertilizers and an adaptation to climate change, translating into sustainable agriculture.

Complex biological systems

In nature, all living organisms are complex systems. For example, a walnut tree (Carya illinoinensis) that covers a surface of 100 m² (10 x10 m) can harbor three thousand species or more, considering the diversity of microorganisms in the soil, those which live in the branches, foliage, the trunk and roots of the tree, on and inside the weeds and pest or beneficial insects. The holobiont and the hologenome are two terms that tell of the set of organisms and genes that make up an individual, respectively, which in turn is part of a population with a defined structure and function. Plants, animals and insects are hosts of many species of microorganisms with their respective genomes (holobionts/hologenomes). Thousands of microbial species, by the billions, live inside humans. Thus, other attributes of the complexity of biological systems are the communication between its elements (organisms-soil-atmosphere), where each one has a bearing on the others, they receive feedback and their responses are non-linear. In addition, no element has the total of information on the system. The system can change dramatically due to the effect of one or a few elements. Systems are open, meaning that they communicate with other systems that surround them and their evolutionary history determines their ability to adapt. Biological systems transform into agricultural systems, using large amounts of energy. Oftentimes, agriculture destroys ecosystems, pollutes soils and bodies of water, leading to ‘unproductive lands’. The concept of ‘unproductive’ contains the anthropogenic element of ‘profitability’; if it is not satisfied: a) the crop is changed, b) land use is changed, or c) the land, of agricultural use, is neglected. Approximately 2 million km² of agricultural lands have been neglected in recent decades (^{Mata-González, 2020}).

The nature of plant-microorganism associations

Symbiotic associations between plants, insects and microorganisms have been allowed to exist for the past 400 million years (^{Poveda-Arias, 2019}). Some of the microorganism-plant interactions worth highlighting are endophytic microorganisms, which live inside plants without causing any harm to them; other microorganisms can live in the rhizosphere (soil around the root), rhizoplane (on the root) and the phylosphere (on the leaf) (^{Sharma et al., 2019}). Nitrogen-fixating symbiotic bacteria or free-living bacteria and mycorrhizal fungi can also be found. These organisms are usually limited by the management of agricultural crops, such as with the excess use of nitrogen, phosphorous and potassium in the soil, the immoderate use of pesticides, the type of tillage, monoculture and crop rotations (^{Guerra-Sierra, 2008}). The high use of synthetic inputs in contemporary agriculture can lead to high yields in crops, but it generally undermines the benefit of organisms that interact with plants. By contrast, natural systems do the opposite. Both the natural systems and organic agroecosystems are more durable and sustainable than the intensive agriculture farming systems. The fragility of the ecosystems has been widely documented. For example, in areas in which certain nitrogen sources contaminate the soil and air, the growth of lichen species is limited, which are the diet of two endangered primate species (^{Wang et al., 2020}).

Bacteria-insect interactions

Inside insects, microorganisms such as bacteria, fungi, nematodes, phytoplasmas and viruses live inter or intracellularly; most of these are beneficial or not harmful, although some are pathogenic or parasitic. The bacteria Wolbachia are widely distributed in arthropods and nematodes and can kill and influence the reproduction of agricultural pest insects and vector insects for human and animal diseases (^{Rodriguero, 2013}). By invading the brains of insects, Wolbachia can affect their learning, memory, mating, feeding and aggregation; hence, its great potential to control insects is considered harmful to humans (^{Bi and Wang, 2020}). For example, Wolbachia invades Trichograma, a parasitoid wasp, and induces differentiated parthenogenesis, with the resulting development of an exclusively female population, which are a parasite to pest insects (^{Rodriguero, 2013}). Beneficial insects can acquire pathogenic microorganisms, which can decimate their populations and persist in all the stages of their life cycle (^{Samaniego-Gaxiola et al., 2019}); likewise, pest insects can also be affected by microorganisms (^{Zimmermann et al., 2013}). The approach is to focus on finding and using organisms that affect harmful organisms in a negative way and beneficial organisms to agricultural crops in a positive way.

Genetics of crops

Crops were originally developed by humans, using selection processes (phenotypical criteria). Modern agriculture is based on the manipulation of plant genetics. However, three aspects make it difficult to use and understand the interaction between the environment and the genetic expression of plants: a) “Jumping genes” or transposons, DNA sequences that move and interact in the genome. In maize, they are found in approximately 80% (^{Eguiarte et al., 2013}); b) the pangenome, or genes different to the rest of the clade; in the case of the grass species Brachypodium distachyon (L.) Beauv., the genes of its population are 61 thousand and each individual has 30 thousand (^{Gordon et al., 2017}); c) a scarce understanding of the genetic regulation of plants in extreme environments, such as the conifers that survived the Chernobyl radiation (^{Geras’kin et al., 2011}). That is, cultivated and native plants still have an enormous potential to detect their genetic and epigenetic characteristics to help them adapt to different types of biotic or abiotic stresses, or to new ways of doing agriculture. The benefit would be the use of local or regional genetic resources without depending on commercial varieties from foreign or multinational companies (H. Cortez in this Special Edition). COVID-19 displayed the danger of depending on inputs with the rupture of supply chains, and with that, the risk of food self-sufficiency.

Endosymbiosis, endophytes, mycorrhizae, parasites and pathogens

Larger organisms (animals, arthropods or plants) interact and host thousands of smaller ones (mainly microorganisms), conforming a unit or consortium called a holobiome, with its respective hologenome. As the knowledge on the interactions between organisms arises, the conceptual terms mix or are modified. Bacteria of the genus Rhizobium and their related species can be considered plant endosymbionts. However, endosymbiosis may indicate that an organism was integrated into another, such as chloroplasts and mitochondria, which integrated to become plant and animal cells, respectively; or bacteria that live inside insect cells (^{Espinosa, 2019}). Likewise, some mycorrhizae (endomycorrhizae) can live inter or intracellularly in plant roots and can therefore be classified as endophytic fungi. When interactions between organisms are harmful to at least one of them, we say there is an antagonism. An insect can be the parasite of plants i.e., live at their expense, causing damage or transmitting viral diseases. Meanwhile, fungi, bacteria, nematodes, and weeds can be phytoparasites and/or phytopathogens (causing diseases) in plants. Animals, weeds and microorganisms themselves have their own parasites and/or pathogens. There is a very fine line between the levels of interaction of a parasite and/or pathogen, from not becoming one or to stop from being one; this is determined by the affecting organism (parasite or pathogen), the organism affected (host) and their surrounding environment (^{Chitnis et al., 2020}; ^{Sugio et al., 2015}).

Endophytes in plants and insects

In nature, microorganisms often have more than one function in different moments. Thus, Metarhizium can be saprobic (feeding off organic residues), entomopathogenic (attacks and kills insects) and endophytic. In turn, Trichoderma can mycoparasite Rhizoctonia and other plant pathogens, but can also be saprobic and endophytic; its metabolism changes in endophytes according to the role they play (^{Sugio et al., 2015}). The seed, the vegetative material, the rhizosphere and the phylosphere are points of entry and propagation of endophytic microorganisms (^{Lata et al., 2018}). These endophytic microorganisms can help plants counteract different types of biotic stresses such as pests, diseases, predators, weeds and invading plants, on the one hand, and abiotic stresses such as temperature, salinity, drought, pH, nutrients and heavy metals on the other. Plants respond to this type of stress by changing their physiology, metabolism and morphology. This can happen when they associate with endophytes, which a) induce plant gene regulation, in a function known as induced resistance (^{Lata et al., 2018}); b) produce beneficial metabolites for plants and harmful to weeds, pests and pathogens; some of these metabolites are phytohormones, antioxidants, alkaloids, terpenoids, derivatives of isocumarin, quinones, flavonoids, chlorinated metabolites, phenol, phenolic acids, and others (^{Kaur, 2020}; ^{Torres and White, 2010}). Other changes caused by endophytes in or around plants are: 1) they act as antagonisms against plant-harming organisms such as fungi, nematodes, bacteria and insects (they parasite, compete, lyse, inhibit, intoxicate, prey); 2) they solubilize nutrients for the plant; 3) degrade plant or crop residues, which improves structural properties (aggregates) and soil fertility.

Endophyte-insect associations can be beneficial or harmful to insects. The microbiota inside the insects is ten times as numerous as the cells of insects. Endophytic bacteria inside the intestines of insects are crucial to them, since they directly or indirectly provide essential nutrients, fixate nitrogen and even synthesize part of their pheromones and allomones, which they use to communicate (^{Poveda-Arias, 2019}). Insects may host microorganisms and viruses, some of which are harmful, inside their intestines or intracellularly. A long list of harmful microorganisms is known to act as pests to agricultural crops, including the codling moth Cydia pomonella; its pathogens, viruses, bacteria, fungi, microsporidia and nematodes were found after analyzing over 20 thousand specimens between larvae, pupae and adults in the years between 1952 and 2012 (^{Zimmermann et al., 2013}). Insects can transfer part of their microbiota to plants (including endophytes) and vice versa, where a gene transfer can occur, to the plant and from the plants to insects (^{Sugio et al., 2015}).

Endophytes and their benefits

The plant Dichanthelium lanuginosum can survive temperatures between 38 and 65 °C when associated to the endophytic fungus Curvularia protuberata (^{Redman et al., 2002}). Leymus mollis, known as “American dune grass”, lives next to beaches. When the plant has an endophytic relation with the fungus Fusarium culmorum, it displays no symptoms of wilt when kept for 14 days in a 500 mM solution of NaCl (^{Rodriguez et al. 2008}). The 300 thousand plant species have one to two main endophytic fungi (^{Kaur, 2020}). Additional applications of endophytic fungi include a) bioremediation, since they accumulate, degrade and detoxify heavy metals in plants; b) biomedicine, from the production of anti-cancer compounds and antibiotics to nanoparticles; c) the production of biodiesel; and d) the production of industrial enzymes (^{Yan et al., 2018}). Trichoderma spp., in addition to being endophytic, produces hydrophobin-type proteins, which, paired with enzymes, degrade PET plastics, which are currently important pollutants worldwide (^{Druzhinina, 2017}).

Trichoderma and Metarhizium

The species of Trichoderma are widely used since, among other beneficial characteristics to plants, their potential to produce plant hormones stands out for stimulating growth in agricultural crops (^{Guzmán-Guzmán et al., 2019}). Since the 1990s, the species of this fungal genus are widely used as a biological control since they inoculate seeds (^{Mukhopadhyay et al., 1992}). In association with Trichoderma harzianum, over 278 volatile compounds were identified, some with a potential for fumigation (^{Siddiquee et al., 2012}). The genus Trichoderma has been estimated to have 400 species, some of which blend all the characteristics of endophytes mentioned, including the characteristics of growth-promoting bacteria (^{Sharma et al., 2019}). Another fungus with a potential for pest control is Metarhizium spp., which has a wide variety of species and is entomopathogenic to a wide variety of insects in Mexico and many other countries (^{Brunner-Mendoza et al., 2019}; ^{Hernández-Rosas et al., 2019}). Metarhizium anisopliae has been used extensively and successfully for pests as important as locusts (Schistocerca gregaria) and grasshoppers (Zonocerus variegatus). With 2.5 x 10¹² conidia/ha, S. gregaria can be controlled under moderate temperatures and in the nymph state of the insect (^{Van der Valk, 2007}).

Beneficial organisms and agricultural sustainability

In addition to the problem of neglecting arable land, there is soil contamination and erosion. Every year, the worldwide use of pesticide per capita is one pound. Alongside this, in Mexico, highly dangerous pesticides are still used which are illegal in other countries that have more rigorous control systems (Bejarano, 2018). The successful use of beneficial organisms in agriculture undoubtedly brings us closer to sustainability. To reach such a goal, the ways of practicing science and technology and their application must be improved. A research agenda is also necessary to use endophytes, nitrogen fixators, insects for pest control and other beneficial organisms for agriculture and human activity. In Mexico, information on entomopathogens for agricultural and forest crops was recently reviewed (^{Pacheco Hernández et al., 2019}). Information was also reviewed for specific genera such as Metarhizium (^{Brunner-Mendoza et al., 2019}; ^{Hernández-Rosas et al., 2019}) and Trichoderma (^{Guzmán-Guzmán et al., 2019}). Additionally, Mexico has a National Agri-food Health, Safety and Quality Service (Servicio Nacional de Sanidad, Inocuidad y Calidad Agroalimentaria) which has technical and biological information in the National Biological Control Reference Center (Centro Nacional de Referencia de Control Biológico), which has an important collection of entomopathogenic fungi. Recently, SADER established a National Genetic Resource Center with microbiological collections of interest to agriculture (Zelaya-Molina and Col. in this Special Edition). Mexico, a leader in Latin America in the application of the biological control in its official pest management model, has a directory of biological control agent-reproducing and commercializing laboratories in Mexico (^{SENASICA, 2020}). Thus, Mexico has over 70 laboratories that produce beneficial organisms for agriculture and their number can be higher if low-scale artisanal productions are included. Ten years ago, the increase in the use of beneficial organisms for agricultural crops in Mexico was envisaged (^{García de León and Mier, 2010}). In Mexico, the activities of the Mexican Biological Control Society (Sociedad Mexicana de Control Biológico), with over 500 members, display the relevance of this sustainable approach: 43 National Conferences in over 30 cities throughout the country; 6,500 talks; 51 national courses and 200 workshops in which over 6 thousand technicians and farmers have been trained (R. Lomelí. 2020. Personal communication). ^{Cotes (2018}) analyzes the current view of the status and potential in the use of beneficial organisms for plants with success stories in pest and disease control, as well as the challenges for the consolidation of biological control.

The current and potential impact of beneficial organisms

The massive adoption and economic impact of beneficial organisms (predator insects, parasitoids, growth-promoting bacteria, entomopathogens and endophytes) are limited in the world, although there are exceptions, such as the forage endophytes in New Zealand, which provide 200 million dollars a year; likewise, the number of patents of beneficial organisms is limited (^{Chitnis et al., 2020}). Mexico has successfully applied biological control with beneficial insects and fungi, the most outstanding of which are the control of locusts Schistocerca piceifrons piceifrons and of the fruit fly Ceratitis capitata Wiedemann. In 2013, Mexico stood out for being the country with the third highest production of Trichogramma spp., but particularly for its megadiversity of beneficial insects, some of which were successfully used to control pests in other countries (^{Williams et al., 2013}). Some of which we can highlight are the genera of the bacteria Wolbachia and of the fungus Trichoderma. The former is strategic for the development of the biological control of pest insects (^{Bi and Wang, 2020}) and the latter stands out for its habitat distribution and versatility for use in agriculture, biotechnology and bioremediation (^{Hu et al., 2020}; ^{Guzmán-Guzmán, et al., 2019}; ^{Sharma et al., 2019}). Appropriately and massively detecting, selecting and using beneficial organisms for cultivated plants would have an impact on one or more of the following components: a) mitigating different types of stress (biotic or abiotic); b) optimization of the use of water and fertilizers; c) reduction in the use of pesticides and fertilizers; d) increase in yield. All this would help reduce damages caused by new weeds, pests and diseases (invasive), as well as the effects of climate change; it would reduce pollution caused by agricultural activities and, in sum, agriculture would become increasingly sustainable (^{Chitnis et al., 2020}; ^{Kaur, 2020}; Sharma et al., 2019; ^{Cotes et al., 2018}; Poveda, 2018; Williams et al., 2013).

Generation of knowledge and innovation

To escalate the beneficial functional relations towards a worldwide sustainable agriculture it is necessary to redirect investigation towards the production of knowledge that helps implement technology that is innovative and applicable to an agriculture, whether of traditional production or an intensive and extensive production agriculture. The laboratory model that currently prevails must be complemented with work on the fields. In the context of COVID-19, the window of opportunity amidst the world’s need for food, as well as the sustainability and food security facing the crisis of supply of inputs required mainly by middle and high technology agriculture must be used to create an agriculture of the future in line with the enormous climate, food and health challenges. Investigation for an avant-garde and sustainable agriculture must include: a) systemic studies of the beneficial organisms-plant relations at a field level; b) a scientific clarification of how such relations work; c) if they work, is it as a holobiom?; d) How does the environment affect functional relations?; e) How is the original holobiom of plants affected by the beneficial organisms-plant relations? And what would be the consequences for plants?; f) Identification of highly specific organisms, beneficial to plants, considering the integration of plant genomes in its genome; g) How would agricultural practices impact the beneficial organisms-plant relations? (^{Chitnis et al., 2020}; ^{Sharma et al., 2019}; ^{Cotes et al., 2018}; ^{Williams et al., 2013}).

Perspectives

Mexico lacks a national beneficial organisms database for agriculture, although the vast official collections are merit worthy (^{SENASICA, 2020}). They could be set up to optimize the study and application of beneficial organisms. Ecological studies at a national scale on beneficial organisms are also necessary, similar to those carried out in China for Trichoderma spp. (^{Hu et al., 2020}). The isolations or strains of microorganisms (including viruses that attack insects), as well as specimens of parasitoid and predatorial insects, should be recorded in a national database with agronomic and ecological information attached to each record. The way to generate investigation, technology and the adoption of farming technology must be consolidated. In this sense, India sets the example with the ‘^{National Agricultural Innovation Project’}, constituted in 2014 with a fund of 257 million dollars and which gathered 850 work groups (investigators, technologists, extensionists and producers). A part of the project focused on species for the biological control of pests and diseases such as Trichogramma, Chrysoperla, Trichoderma and Pseudomonas. The finding of Chrysoperla zastrowi sillemi is worth highlighting, since endophytic bacteria and fungi were found which had the ability to confer resistance to insecticides, desiccation and temperature (^{Hemalatha et al., 2014}; ^{Hemalatha, 2015}). With four C. zastrowi sillemi larvae in a greenhouse, the amount of Myzus persicae per tomato plant was kept at 0.5 or less, as well as one whitefly Bemisia tabaci or less (^{Nair et al., 2020}).

Communication between researchers, producers and marketers of biological agents is crucial, and particularly the exchange of experiences, microorganisms and beneficial insects between researchers. This would require a regulation of the rights that researchers and institutions may have on the organisms. In addition to organisms that are beneficial to agriculture, organisms useful to other areas such as medicine, bioremediation, etc. must also be explored. The creation of public policies that lead to a national research agenda where public and private institutions and producers participate is also urgent. Internationally, there is a growing interest towards promoting comprehensive research and development systems that transcend academic interest. Only in this way will there ever be an impact on sustainable agriculture models (^{Chitnis et al., 2020}; ^{Sharma et al., 2019}; ^{Cotes et al., 2018}; ^{Williams et al., 2013}).

Final considerations

At a field or greenhouse level, we can realize the impact of a stress factor on crops and how they affect their relations with pests and diseases (^{Polack, 2008}; ^{Samaniego et al., 2008}). Therefore, gathering information on crop management is crucial to apply and improve biological control and obtain other benefits from organisms with endophytic abilities. We may have to consider gene modification and expression (epigenetic) induced by endosymbionts, as well as its impact in the holobiom microorganisms-insects-plant (^{Chitnis et al., 2020}; Poveda, 2019; ^{Sugio et al., 2015}). For example, the bacteria that live intracellularly in aphids, inside cells called bacteriocytes, lose a large portion of their genome (^{Espinosa, 2019}). In rice, pea, pigeon pea, chickpea, maize, soybean, tomato and wheat, over 100 genera of beneficial endophytic fungi have been found. Up to 60% of them were found in one crop and 8% (Alternaria, Aspergillus, Chaetomium, Cladosporium, Fusarium, Penicillium, Piriformospora and Trichoderma) in all eight crops. In this way, there is a combination of specific fungi versus generalists (^{Rana et al., 2019}). Therefore, it is common to find beneficial or generalist endophytes, generally common soil fungi, except for Piriformospora indica (^{Liu et al., 2020}). This fungus has a wide variety of host plants that it protects from phytopathogens, this could be evaluated in Mexico as a beneficial endophyte, likewise Trichoderma spp. isolations from different collections in the country. The specificity of endophytes goes beyond their ability to associate with plants; it represents an enzymatic functional diversity, typical of an adaptation to a plant lifestyle (^{Knapp et al., 2018}). The experience of our laboratory suggests that we can find large amounts of endophytes, most of which are abundant in some soils. A quick way of knowing if they have a possible relation with roots is to make them grow in a conventional medium (PDA) and then place seeds. The seeds with an affinity to the fungus germinate and grow roots in the culture medium (Figure 1). In this way, we would find a large number of fungi with an affinity to cultivated plants in a country as megadiverse as Mexico. Seeds and seedlings can be inoculated with the selected fungi, which would provide a very large number of plant responses. At the end of the cultivation cycle, it would be possible to isolate an inoculated fungi if it has an enfophytic activity. (Figura 2) (J. Samaniego. Data not published),

The beneficial interactions model of the organisms should be emulated among all the sectors interested in this alternative. Researchers should be able to exchange isolations, experiences and support regional collaboration models. Businesses that reproduce microorganisms for biological control and biofertilizers could sell them. All this within a framework that protects coyprights. The final purpose of the investigation is to generate technology for the farmer. Perseverant and cooperative work in research usually results in an economic impact. The entomopathogen Ophiocordyceps sinensis, possesses properties in medicine, which makes its value worth 1.2 million pesos per kilogram, additionally, it benefit the scientific and industrial sectors (^{Li et al., 2019}).

The sustainability aims to maintain human health, that would allow a better facing of this and further pandemics, by producing food that strengthen the immune system. Moreover, the food production would require less supplies or a better management of these attenuate the abiotic and biotic stresses, all of these through the association of beneficial organisms to the plants.

Figure1 Evaluation of endophytic fungi in germination of alfalfa (Medicago sativa) and watermelon (Cucumis melo) seeds in PDA media. A. Germination of the alfalfa and watermelon seeds on different fungi colonies. B. Germination of alfalfa on colonies of Trichoderma sp. in water-agar. C. Alfalfa seedings on fungi colonies with rooth growth on the media. E. Germination of alfalfa seeds, withouth previous disinfestation with NaOCl. F. Germiantion of disinfected seed.