Agriculture is an economic activity that deals with the scientific production of crops to address world hunger. Food is a fundamental right of humans; therefore, it is the utmost concern of all countries to increase their agricultural production, as the global population is expected to reach nearly 10 billion by 2050 (Gill and Garg, 2014; Dutta et al., 2022a). However, one of the major challenges encountered by agriculture today is the sustainable production of high-quality food in a sufficient quantity to meet the needs of the producer and consumer. Among the various biotic and abiotic factors contributing to the economic yield loss of crops, destruction due to diseases caused by filamentous fungi is of foremost importance (Singh, 2014). Soil-borne plant pathogens lead to a significant reduction in crop yield by causing diseases such as die-back, wilting, and root rot. They usually target the roots to enter into the plant system and directly influence water and nutrient uptake capacity. Soil-borne diseases therefore have a direct negative impact on plant growth and development (Dignam et al., 2022). The management of soil-borne plant diseases is a cumbersome task. Large amounts of chemical pesticides are administered early in the farming process to counteract these phytopathogens. The use of chemical pesticides, however, has a negative impact on the environment, such as residual toxicity and soil pollution. Therefore, the biological management of plant diseases with different bacterial and fungal biocontrol agents is considered a safer option. Trichoderma, a soil-inhabiting ascomycete fungus, is widely used for its versatile plant growth-promoting (PGP) and biocontrol activity. First described by Persoon (1794), the genus Trichoderma outraces phytopathogens in the competition for space, nutrients, antibiosis, and mycoparasitism (Mukherjee et al., 2013). Furthermore, Trichoderma is also known to colonize plant roots, to enhance plants’ systemic defenses, viz., systemic acquired resistance (SAR) and induced systemic resistance (ISR), and to promote plant growth by modulating the phytohormonal blend. To do so, Trichoderma needs to interact and establish a good relationship with the host plant. Proteins or peptides are the communicating molecule in any plant–fungus interaction. Plants and fungi communicate and perceive their surroundings via the secretion and perception of different peptides. Understanding the soluble secretome of Trichoderma will shed light on the mechanisms of molecular crosstalk between plant roots and Trichoderma, and will explain the mechanism behind PGP and biocontrol activities.

In the early 1930s, the biological control potential of Trichoderma was realized. Weindling, while working with T. lignorum and Rhizoctonia solani, observed that the mycelial growth of R. solani was inhibited by the profuse mycelial growth of Trichoderma. Microscopic observation led to the discovery of a new phenomenon, whereby the hyphae of T. lignorum coil around the hyphae of the phytopathogen and penetrate them, which subsequently leads to complete dissolution of the host cytoplasm. The mechanism of parasitization of another fungus by Trichoderma was named mycoparasitism by Weindling (1932). The discovery of the mycoparasitic nature of Trichoderma led a great volume of work on the subject by many researchers. The studies carried out led to the discovery of different biocontrol mechanisms exhibited by fungi from the genus Trichoderma. Genome profiling of three Trichoderma species, viz., T. virens, T. atroviride, and T. reesei, by Mukherjee et al. (2012) has opened avenues for understanding the molecular mechanism behind their advantageous biocontrol activities. Mycoparasitism, competition with other soil inhabitants/invaders, and antibiosis are the major modes of action for the biocontrol activity of Trichoderma (Zhang et al., 2021). Synchronization between mycoparasitism and antibiosis is necessary for the proper functioning of this biocontrol agent (BCA) (Keswani et al., 2014). Moreover, the host defense activation triggered by Trichoderma is a key part of its ability to protect plants against several phytopathogens. Therefore, it can be said that a combination of competitive exclusion, antibiosis, mycoparasitism, and induced systemic resistance ( Figure 1 ) is crucial for Trichoderma-mediated disease suppression/management (Sharma et al., 2017). Trichoderma is a very fast-growing BCA that rapidly colonizes the spermosphere and/or rhizosphere, thereby providing protection to germinating seeds against major soil-borne, seed-borne, and air-borne plant diseases (Mukherjee et al., 2022).

The emergence of the era of molecular science in the 1940s and 1950s, and its subsequent progress, with the development of different biotechnology tools, made it possible for scientists to isolate, study, and determine the chemical composition of individual genes present in any organism, and ultimately paved the way for whole-genome sequencing. The ability to map and study genes present in a genome made it easier for scientists to understand how genes are assembled in a genome and how they perform their function. In this context, the development of evolutionary trees was also fine-tuned by the detailed knowledge obtained from the understanding of genomics (Merrill and Mazza, 2006). The comprehensive study or global assessment of a set of molecules is referred to as “omics”. Next-generation sequencing of genetic materials and the development of other high-throughput technologies has led to availability of omics data worldwide. The first omics to appear was genomics, which deals with the study of the whole genome of an organism (Hasin et al., 2017). Different omics, viz., genomics, transcriptomics, proteomics, and metabolomics, contribute to the wealth of omics data available publicly across the globe ( Figure 6 ). Trichoderma reesei was the first species of Trichoderma to have its whole genome sequenced (Martinez et al., 2008). Subsequently, the complete genome sequencing of many species of Trichoderma was carried out, and the genomic information is available from the NCBI (National Center for Biotechnology Information) GenBank database ( Table 2 ).

Sanger expressed sequence tag (EST) projects have made transcriptomics studies of Trichoderma–plant interactions easier (Steindorff et al., 2012; Silva et al., 2019). In addition, a transcriptomic study of Trichoderma genes present in the fungal cell wall can be obtained using high-throughput techniques such as suppression subtractive hybridization (SSH) (Vieira et al., 2013). Furthermore, a combined omics strategy can be adopted for an in-depth study of Trichoderma–plant/pathogen interactions ( Figure 6 ).

Trichoderma, being a beneficial microbe, has attracted the attention of researchers, who have studied how it adapts to plant root colonization. The upregulation of genes responsible for the formation of infection structures was observed in an early transcriptomic study of Trichoderma colonizing tomato roots in a hydroponic system (Samolski et al., 2009). Similarly, Lawry (2016) observed the presence of an appressorium-like structure in a Trichoderma virens–maize hydroponic system that helped the biocontrol agent penetrate the plant cell wall and form an intercellular infection peg. The infection pegs possess structures similar to a haustorium, thereby indicating intracellular colonization of maize roots by T. virens. Moreover, forced penetration, by pushing away the outer cell layer of the epidermis, was observed in maize grown in T. virens-inoculated soil, and may be considered as another root colonization mechanism of Trichoderma. Rubio et al. (2014) reported a decrease in nutrient and carbohydrate metabolism activity in plants in response to hyphal attachment of Trichoderma. After 20 h of interaction between Trichoderma and tomato grown in a hydroponic system, Rubio et al. (2012) observed the differential regulation of genes in Trichoderma as a response to the host’s fluctuating behavior. It revealed an upregulation of Trichoderma genes involved in carbohydrate metabolism, nutrient exchange with the plant, the generation of building blocks, and cell wall synthesis, and a downregulation of genes that indicate a sufficient availability of nitrogen. Furthermore, the upregulation or downregulation of genes in Trichoderma during root colonization of either tomato or maize plants is greatly regulated by the host itself. In a T. virens–maize co-culture system, the genes that are mostly upregulated belong to classes such as the glycosyl hydrolases (GHs), oxidoreductases, and small secreted proteins, and the symbiosis-related invertase TvInv (Vargas et al., 2009). The gene most preferentially expressed in T. virens during its interaction with tomato was revealed to be a secreted quino-protein, glucose dehydrogenase. Several studies on the secretome of different species of Trichoderma co-cultured with plants have reported an increased expression of genes encoding glycosidases and peptidases during the initial phase of their interaction (Lamdan et al., 2015; González-López et al., 2021). Reduction in tomato root colonization by a T. harzianum mutant with a silenced thpg1 gene encoding endopolygalactouronase indicates the probable role of fungal glycosidases and peptidases in plant–Trichoderma interactions. Therefore, it can be said that the lytic enzymes released by Trichoderma during the initial phase of their interaction with plants is essential for disintegrating cell wall components to aid in the successful colonization of plant roots (González-López et al., 2021). Furthermore, during the first 24 h of interaction, the genes encoding a group of antioxidant enzymes were found to be exclusively expressed, which is necessary for ROS detoxification, and therefore demonstrates Trichoderma’s strategy of adaptation to the highly reactive environment of plants (González-López et al., 2021). However, there is still a need to perform more function-oriented experiments to obtain a clear understanding of the biochemical significance of host specificity at a transcriptome level. Overall, it can be summarized that the host and Trichoderma appear to coordinate their counterattacks, and Trichoderma has several genes for secreted proteins that apparently play a key role in determining its ability to survive in the complex rhizosphere ecosystem.

Proteomic study of the secretome of Trichoderma revealed that 3.5%–6.0% of total proteins are released via the type II secretion system into the apoplastic space of the plant cell, which is also known as the soluble secretome of Trichoderma. Gene ontology studies of the soluble secreted proteins of Trichoderma have revealed the range of different functions exhibited by these proteins, which are primarily CWDEs, cell wall adherence proteins (such as adhesins, hydrophobins, and tandem repeats), effector-like proteins, proteins determining host surface attachment and recognition, and proteins involved in secondary metabolisms (Mendoza-Mendoza et al., 2017). An effort is made here to briefly discuss the literature available on the soluble secretome of Trichoderma with regard to plant root colonization and its role in the biological control of plant diseases.

In every plant–microbe interaction, the host cell wall is at the forefront and so is the basal defense. Therefore, it is essential that the micro-organisms digest cell walls by releasing CWDEs in order to break through to the host system. Plant CWDEs are considered a major source of communication molecules and belong to CAZymes groups. GHs essentially digest plant cell walls and facilitate fungal entry into the host tissue. A study conducted with different species of Trichoderma revealed that T. harzianum and T. guizhouense secrete a higher number of CAZyme modules than other Trichoderma species. This may be indicative of their larger genome size and/or their particular behavior in the competitive environment of soil and when interacting with plants and pathogens (Li et al., 2013). In soil, Trichoderma releases a lignocellulolytic enzyme that helps it to live a saprophytic life. However, in the presence of host root exudates they respond differently, synthesizing and secreting CWDEs (Cragg et al., 2015). Harman et al. (2004) reported two glucosyltransferases (GTs) from the soluble secretome of mycoparasitic fungi T. virens and T. atroviride.

The soluble secretome of Trichoderma contains a significant amount of CWDEs. They are responsible for alerting the plant immune system to the presence of an invader. As reported by Avni et al. (1994), inactive cellulase and xylanase were the first MAMPs obtained from Trichoderma. Furthermore, CWDEs cause damage to the plant cell wall, thereby generating DAMP signals. A study of T. harzianum–root interaction in Arabidopsis and tomato led to the discovery of the first DAMP, which corresponds to the oligogalactouronides produced by the enzymatic activity of CWDE endopolygalacturonase ThPG1 in T. harzianum, which was found to be capable of inducing systemic defense in the plants (Moran-Diez et al., 2009). In a study conducted by Baroncelli et al. (2016), the expression of two endo-polygalcturonase genes (viz., TvPg1 and TvPg2) from T. virens I10 was examined during the interaction with tomato roots. The results revealed that, while interacting with, in particular, host roots or pectin, expression of TvPg1 was induced, whereas TvPg2 was later expressed constitutively. According to Sarrocco et al. (2017), this constitutively produced endopolygalacturonase was responsible for eliciting ISR in the host. Similarly, the direct activity of plant chitinases or the mycotrophic nature of Trichoderma against rhizospheric fungi yields chito-oligosaccharides, which can also function as DAMPs in the activation of systemic plant immunity (Woo et al., 2006). Apart from inducing plant immunity by generating MAMP and DAMP signals, CWDEs also play an important role in determining the efficient colonization of roots by Trichoderma. They achieve this by either increasing the plasticity of the host cell wall or causing irreversible deterioration of the cell wall structure.

As the fungal cell wall comprises mainly chitin, glucan, and proteins, mycoparasitism by Trichoderma involves the extensive use of CWDEs, viz., chitinases, glucanases, and proteases ( Table 3 ). Use of a Trichoderma microarray to study the transcriptomic changes of genes in T. atroviride overgrown on a Verticillium dahliae colony revealed that there was total 143 differentially regulated genes (almost 98%) that belonged to the T. atroviride genome. The upregulated genes were all from classes of CAZymes and proteases, viz., serine, aspartic acid, and metallopeptidases genes that are crucial in weakening and disintegrating the fungal host cell wall (Morán-Diez et al., 2019). Therefore, it can be said that the differentially regulated genes of T. atroviride are unequivocally associated with the mycoparasitic and antagonistic activity against the targeted pathogen.

It has been reported that the Trichoderma genome harbors a greater number of genes encoding chitinolytic enzymes, which is attributed to Trichoderma’s mycoparasitic nature. Fungal chitinases belong to the GH18 and GH20 families. GH18 chitinases can be further categorized into subfamilies A, B, and C. It has been observed that genes encoding chitinases from GH18 are significantly expanded in T. atroviride, T. asperellum, T. atrobrunneum, T. gamsii, T. harzianum, and T. virens (Kubicek et al., 2011). Chitin and chitosan (a partial or complete deacetylated derivative of chitin) comprise the chitinous layer of fungal cell wall. Chitosan in mycoparasitic fungi such as Trichoderma plays an important role in the scavenging of ROS produced by parasitized fungi. Kappel et al. (2020) observed that out of six genes encoding chitin deacetylase, the deletion of genes cda1 or cda5 in T. atroviridae led to severely impaired mycoparasitic ability. This result indicates that a decrease in or absence of chitin deacetylase enzymes results in a low level of chitosan in Trichoderma, and, therefore, the Trichoderma is not protected from ROS (Mukherjee et al., 2022). Further study led to the discovery of cell wall remodeling in T. atroviridae during mycoparasitic interaction via the upregulation of all six genes encoding chitosanase, especially toward the later stage of interaction. One interesting finding made during this study by Kappel et al. (2020) was CHS8, which is called as a hybrid synthase due to its similarity to both chitin synthases and hyaluronan synthases, and can utilize both UDP-N-acetylglucosamine and UDP-d-glucuronate as substrates. The authors, therefore, speculated that CHS8, along with CDA1, forms a chitin glycol-polymer layer that protects the Trichoderma cell wall during mycoparasitic interactions (Kappel et al., 2020).

The enzymes α- and β-glucanase are necessary for the deconstruction of the glucan layer. Fungal α-1,3-glucanases are members to the GH71 family. T. harzianum and T. asperellum explicitly secrete the exo-α-1,3-glucanases AGN13.1 and AGN13.2, respectively, in the presence of the Botrytis cinerea cell wall. Enzyme AGN13.1 is found to possess lytic properties against fungal cell walls and exhibit antifungal activity (Mukherjee et al., 2022).

β-1,3-Glucanases are classified into GH families, viz., 16, 17, 55, 64, and 81. The mycoparasitic Trichoderma genomes comprise a large number of genes encoding GH55 and GH64 family members (Kubicek et al., 2011). They play a significant role in the mycoparasitization of oomycete fungi (which have a cell wall composed of cellulose and β-1,3- and β-1,6-glucans). A study of T. virens mutants in which the bgn3 gene, encoding β-1,6-glucanase, is overexpressed found that such mutants exhibited enhanced antagonism toward Globisporangium ultimum, whereas mutants overexpressing the genes for both β-1,3-glucanase and β-1,6-glucanase were found to exhibit enhanced inhibition of G. ultimum (Djonovic et al., 2007).

Proteases are an important group of enzymes released by Trichoderma in the event of mycoparasitism. The differential regulation of several protease genes of Trichoderma is reported during mycoparasitism (Mukherjee et al., 2022). Overexpression of the T. atroviride prb1 gene (encoding protease) reportedly provides increased protection against R. solani (Pozo et al., 2004). Cortes et al. (1998) observed that expression of the prb gene was induced before contact with the fungal host. Further study of gene behavior in nitrogen-limited conditions led to the finding that the promoter region of the prb gene contains a binding site for transcriptional activator of nitrogen catabolite-repressed genes, viz., ARE1 (Olmedo-Monfil et al., 2002; Mukherjee et al., 2022). These findings caused Druzhinina et al. (2011) to hypothesize that, in the early stage of mycoparasitic interaction, the activity of proteolytic enzymes results in host-derived nitrogenous products, which are responsible for the activation of mycoparasitism-relevant genes via their binding to nitrogen sensors present on the Trichoderma cell surface.

Effectors released during Trichoderma’s interactions with plants or fungi participate in ROS scavenging, chitinase and glucanase production, fungal cell wall masking, protease inhibition, and the prevention of defense alarm activation in neighboring cells colonized by the invader (Rabe et al., 2013; Lanver et al., 2017). A study conducted by Mendoza-Mendoza et al. (2017) revealed the presence of 70–123 effector proteins in the soluble secretome of Trichoderma. However, not all these effectors possess a clear functional domain. Some of the effector proteins with known functional domains are discussed briefly herein.

Common in fungal extracellular membrane is a protein domain containing eight cysteines, which distinguishes it characteristically from other known cysteine-rich proteins. CFEM domain proteins were first discovered in rice blast pathogen Magnaporthe grisea (Kulkarni et al., 2003) and are known to play important roles in fungal pathogenicity. The functions of CFEM domain proteins include plant-surface sensing, appressorium development, asexual development (Sabnam and Barman, 2017), iron assimilation (Nasser et al., 2016), and redox homoeostasis (Kou et al., 2017). Fifty soluble secreted proteins of Trichoderma have so far been found to contain CFEM domains.

In an experiment on a Trichoderma–maize co-culture conducted in a hydroponic system, a decreased abundance of several CFEM-containing secreted proteins was observed. On developing deletion mutants for two genes encoding CFEM domain proteins with IDs 92810 and 111486 (Joint Genome Institute (JGI) v2.0), Lamdan et al. (2015) observed an increased ISR response against necrotic phytopathogens. They suggested that an increased degradation or sequestering of CFEM domain proteins by host roots could be the reason for their loss of abundance in a Trichoderma–maize co-culture system. However, further study of CFEM domain proteins is needed to reveal their modeof action in Trichoderma–plant or Trichoderma–phytopathogen interactions.

Chitin, a homopolymer of N-acetyl-d-glucosamine, represents the second most abundant organic matter after cellulose. Chitin is widely distributed in fungi as a major component of the cell wall, but is absent in plants. The presence of chitin in the plant system is recognized by specific lysin motif (LysM)-containing pattern recognition receptors (PRRs) in the plant cell surface, which trigger an innate immune response in plants (Marshall et al., 2011). The absence of these PRRs compromises the plant’s defense against fungal pathogens. Therefore, the plant’s ability to perceive chitin is very important in recognizing phytopathogenic fungi. However, successful plant colonizers have evolved strategies that overcome chitin-induced defense in plants. Alteration of cell wall composition and release of LysM-like effector proteins are some of the strategies adopted by micro-organisms. LysM-like effectors released by plant colonizers bind to the free chitin released in the plant apoplastic space during fungal growth and mask the colonizer’s presence. In this way, they overcome chitin-induced plant defense. Genomic study of mycoparasitic and endophytic Trichoderma has revealed that they contain an increased number of genes encoding LysM-containing secreted and non-secreted proteins as well as chitinases. These proteins help in the penetration and establishment of Trichoderma within the plant system by binding themselves to the fungal chitin and thereby avoiding ligand–PRR binding (Hermosa et al., 2013). Moreover, it has also been suggested that proteins containing a LysM domain may provide a mechanism of self-protection against the Trichoderma’s own chitinases (Gruber and Seidl-Seiboth, 2012).

Hydrophobins are small, unique, surface-active fungal proteins with the ability to form an amphipathic membrane at the interface of hydrophilic and hydrophobic environments. Their β-structured core is composed of eight highly conserved cysteine residues linked by four disulfide bridges. Hydrophobin proteins have a large exposed hydrophobic area, which explains their high surface activity (Linder et al., 2005; Bayry et al., 2012). Class I hydrophobin molecules form rodlet layers on the fungal cell wall by organizing themselves into a highly insoluble amphipathic membrane at the junction of the hydrophilic fungal cell wall and the hydrophobic environment. Class II hydrophobins form micro-aggregates to give rise to dimers and tetramers in a rodlet-like structure (Mendoza-Mendoza et al., 2017). Kubicek et al. (2008) carried out a comparative evolutionary study on class II hydrophobins produced by the ascomycetes group of fungi and noted that the genus Trichoderma ranked first in number and diversity of class II hydrophobins. Guzman-Guzman et al. (2017) reported that a class II hydrophobin, viz., TVHYDII1 of T. virens, contributes to the antagonistic activity of T. virens against R. solani and promotes Arabidopsis root colonization by Trichoderma. Huang et al. (2015) observed an up-regulation in hydrophobin synthesis and secretion in T. asperellum when placed in a 1% Alternaria alternata cell wall and 5% A. alternata fermentation broth, which is indicative of hydrophobins’ role in mycoparasitism. Microarray analysis of T. virens T87 genes revealed that genes encoding hydrophobins were largely downregulated during Trichoderma–tomato interaction (Rubio et al., 2012) and found to have a negative effect on the growth and development of tomato plants in in vitro conditions. This result may be indicative of limited root attachment of T. virens T87 due to fewer hydrophobins, affecting its interaction with tomato plants. Interestingly, Przylucka et al. (2017) have observed upregulated HFB7 genes of T. virens in interactions with tomato. T. harzianum secretes QID74, which is a hydrophobin-like cell wall protein with a high molecular mass. It is particularly involved in fungal cell wall protection, adherence to the host cell, and modification of the host root architecture by increasing lateral roots growth, which, in turn, ensures increased nutrient uptake. Effective utilization of these nutrients results in increased plant biomass, and promising results have been obtained in cucumber and tomato plants (Samolski et al., 2012).

Ceratoplatanins (CPs) are non-enzymatic unique fungal proteins similar to plant expansin proteins. Trichoderma CPs bind to chitin (Pazzagli et al., 2014), which may be helpful in opening the physical spaces of the parasitized fungal cell wall. Similarly, during colonization of the host plant, the behavior of CP proteins might be helpful in masking fungal cell wall chitin from detection by the host plant’s receptors (Quarantin et al., 2016). CPs are also known as eliciting plant response-like proteins (EPLs) due to their role in the induction of SAR in plants (Gaderer et al., 2014). According to Gao et al. (2020), the number of EPL-encoding genes in Trichoderma species is either three or four. During T. harzianum–S. sclerotiorum interaction, the role of EPL1 was found to be significant for the expression of genes related to mycoparasitism and coiling around S. sclerotiorum. Moreover, EPL-encoding genes found to downregulate the expression of virulence genes present in B. cinerea necessary for botrydial biosynthesis. Therefore, EPLs have two major functions in Trichoderma–pathogen interaction, viz., the expression of mycoparasitism-related genes and protection of Trichoderma from secondary metabolites produced defensively by pathogens (Mukherjee et al., 2022).

In Trichoderma, the Sm1 gene encodes a small, secreted protein belonging to the CP family. Sm1 gene abundantly expressed throughout fungal development. Specific growth conditions modulate the expression of the Sm1 gene in Trichoderma. Studies conducted by Vargas et al. (2011) concluded that the detection of sucrose-rich plant root exudates and their trafficking activates the expression of Sm1 in T. virens. Djonovic et al. (2006) demonstrated the role of Sm1 in T. virens as a non-enzymatic effector of plant defense. In addition, purified Sm1 protein was observed to trigger ROS production, thereby eliciting local and systemic resistance in the plant. Furthermore, these proteins are found to have no phytotoxic or antimicrobial function. Trichoderma has a wide host range, and therefore its interactions with its hosts have diverse consequences. Salas-Marina et al. (2015) observed that Sm1- and Epl1-deleted mutants of T. virens and T. atroviride led to decreased systemic resistance in treated tomato plants, and overexpression of these genes resulted in enhanced protection against phytopathogens. In a tripartite interaction involving T. virens Gv29-8, maize, and Colletotrichum graminearum, Crutcher et al. (2015) observed an enhanced expression of Sm2 protein by T. virens. The use of mutants developed by deletion of the Sm2-encoding gene revealed that they were able to induce same level of ISR in maize plants; however, the root colonization ability of T. virens was found to decrease significantly. Conversely, a study on the interaction of Sm1-deleted mutants of T. virens, I10 maize, and Cochliobolus heterostrophus revealed a decreased level of ISR, and an Sm1- and Sm2-deleted mutant caused a more severe reduction in the plant’s defense response (Gaderer et al., 2015). The diverse responses obtained from these tripartite interactions could be due to the different lifestyles of the phytopathogens used for the study. The plant’s immune response to biotrophs, hemibiotrophs, and necrotrophs upon infection could determine which Trichoderma elicitors/effectors are deployed. Indeed, the activity of the same Trichoderma-derived effector could be altered by the host plant’s response, thereby explaining some of the distinct actions of Sm1 and its paralogs depending on the three-way interaction.

Swollenin is a soluble secreted protein first described in T. reesei. Swollenin and its orthologs are structurally characterized by the fungal carbohydrate-binding domain (CBD) in their N-terminal, which is followed by a region with domains 1 and 2, similar to plant expansin (Saloheimo et al., 2002). The presence of CBD in their N-terminal helps them to bind to the carbohydrate molecules present in the plant cell wall, and facilitates access to and colonization of the plant system. Brotman et al. (2008) observed that TasSwo—a swollenin protein secreted by T. asperellum—recognizes and binds to the cellulose present in the plant cell wall via the CBD and alters the architecture of the plant cell wall in favor of root colonization by Trichoderma. Furthermore, the authors demonstrated that the CBD present in these proteins acts as a MAMP by inducing plant-innate immunity in cucumber to phytopathogens such as Botrytis cinerea and Pseudomonas syringae.

Genomic study of Trichoderma has revealed the presence of several proteins with the cell wall stress-responsive component (WSC) domain. Although no direct information is yet available on how these proteins help Trichoderma in their interactions with plants or pathogens, similar proteins encoded in Trichoderma genome are also reported in other plant-beneficial endophytes. For instance, in Piriformospora indica, the WSC domain protein FGB1 performs the function of plant immunity suppressor by altering its cell wall composition and properties, and therefore aids its establishment within the host plant (Wawra et al., 2016). Moreover, as reported by Tong et al. (2016), these proteins may have a role in promoting cellular resistance, cell wall disruption, high osmolarity, the production of metal ions (Mg²⁺, Zn²⁺, Fe²⁺, Ca²⁺, Mn²+, and K⁺), and oxidation (Silva et al., 2019). In addition, under stressed conditions, WSC domain proteins, viz., FGB1 and WSC3, may be involved in β-glucan remodeling in the fungal cell wall (Wawra et al., 2019). A comparative secretome analysis of Trichoderma under salt stress conditions revealed that, in the presence of its plant host, the expression of WSC domain proteins in Trichoderma decreases, which may be indicative of the benefits derived by the fungus from its symbiont (i.e., the plant) through intensified root colonization (Rouina et al., 2022).

Other than the above-discussed secreted proteins, there are certain proteins identified in Trichoderma genomes, the function of which are not yet known. The presence of genes for different proteins, e.g., necrosis-inducing polypeptides (NPP1), killer-like toxins, GLEYA adherence proteins, and fungal ribonucleases (RNAses), are reported in different Trichoderma genomes. The expression of some killer-like toxin protein-encoding genes, such as KP4, hinders plant growth (Allen et al., 2008); however, as reported by Allen et al. (2011), the inclusion of this gene in transgenic plants is effective in protecting the plants from phytopathogens. Similarly, across Trichoderma species, the number of secreted GLEYA adhesin protein differs. According to previous studies, T. guizhouense harbors the maximum number of such proteins, i.e., three; T. atroviride, T. gamsii, and T. parareesei secrete two proteins; and T. harzianum, T. virens, and T. reesei contain only one such protein. The presence of necrosis-inducing proteins (NPP1) in both mycoparasitic and saprophytic Trichoderma genomes and their role in plant interaction is still not clear. However, it has been speculated that NPP1 genes and their expression are not always related to necrosis in the host plant, but may also play a role in fungal growth and sporulation (Santhanam et al., 2013). Recently, the use of RNA-interacting proteins and RNA by fungi has been reported in the establishment of successful interactions with the host plant (Spanu, 2015). Among three different families of RNAses present in fungi, viz., non-specific RNases, RNase T1, and RNase T2, Trichoderma genomes are reported to express two RNAse families, i.e., RNase T2 and non-specific RNases. Although the T2 family RNases are known to perform functions such as nutrient acquisition, phosphate solubilization, defense against phytopathogens, self-incompatibility, and senescence (Deshpande and Shankar, 2002); however, their role in establishing interaction with plants is still not known.

Trichoderma is widely used across the globe due to its biocontrol and plant growth-promoting abilities. The interactions of Trichoderma spp. with host plants and pathogens at a molecular level will provide insights on the mechanisms that make Trichoderma a superior biocontrol agent. Mycoparasitism by Trichoderma is a complex process; therefore, a comprehensive study at the gene level is important to understand how the BCA safeguards itself from the defense strategies adopted by the parasitized fungi. Moreover, knowledge of secondary metabolites secreted by Trichoderma during their interaction with either the plant host or fungal host may be helpful in formulating effective bioactive molecule-based formulations that can provide enhanced protection to plants for a longer time. An understanding of the molecular dialogues between the host plant/fungus and Trichoderma is important to realizing the full potential of Trichoderma as a biocontrol agent.

MM prepared the original draft, and PD reviewed and edited the article. All authors contributed to the article and approved the submitted version.