1. Introduction

Land plants live in constant interaction with other organisms, predominantly microorganisms, which have different life strategies ranging from symbiosis to necrotrophic pathogenesis. Therefore, plants have to constantly negotiate with “enemies” (pathogens) and “allies” (symbionts, as well as beneficial epiphytes and endophytes). The colonization of a plant by various beneficial and harmful organisms is governed by a complex network system that has been developed in long co-evolution and which includes a molecular dialog between the interacting partners ^[1][2].

There is a constant signal exchange between the host plant and the organisms which colonize it. In particular, different effector proteins are produced by plant pathogens, secreted into the host plant tissues, which help to overcome plant defense system and/or to modulate host plant physiology ^[3][4]. The effector proteins also play an important role in the colonization of the plant by symbiotic organisms, e.g., mycorrhizal fungi ^[5] or nitrogen-fixing bacteria ^[6]. In its turn, a host plant can recognize the molecules secreted by a pathogen and activate the immune response by producing the proteins with antimicrobial activity and toxic compounds ^[1][7].

The production of peptide phytohormones can be used by plant-colonizing organisms for different purposes. First, the effectors mimicking peptide phytohormones can help overcome the defense systems of host plants and increase the efficiency of colonization, as in the case of the PSY-like bacterial peptide RaxX ^[8]. Second, plant peptide hormone mimics can manipulate the growth of plant tissues to create the habitat and food source for the colonizer, as it was shown for the CLE and IDA peptides of plant-parasitic nematodes ^[9]. Likewise, the CLE peptides produced by arbuscular mycorrhizal fungi stimulate lateral root development thereby increasing mycorrhization of the host plant ^[10].

Thus, according to the recent data, peptide phytohormones are widespread outside the plant kingdom and can be used by organisms with different life strategies to interact with plants.

2. Peptide Phytohormones from Plant Pathogens: Divide et impera

However, some plant pathogens are able to use phytohormones for their own purposes, modulating the level of active phytohormones or the response to them in the host plant ^[11][12][13]. In particular, the ability to produce peptide phytohormones, which are used to change the growth of the host plant and to suppress its defense reactions, has become widespread among the phytopathogens from different kingdoms of the living world—bacteria, fungi, and animals (namely, nematodes) ^[14][9].

To date, the nematode-derived peptide phytohormones of the CLE, CEP, and IDA families have been identified ^[15][9]. The precursors of these peptides are secreted into the root cells after nematode penetration in the host plant, where they undergo processing in the plant body, and the resulting mature peptides are able to interact with plant receptors and activate downstream signaling pathway leading to growth response. The expression of nematode genes encoding peptide phytohormones is required for the successful invasion of the host plant by nematodes ^[16][17][18].

The plant pathogenic fungi can manipulate the development and immune response of the host plants via complex and diverse mechanisms, including the production of IAA and cytokinins ^[19], as well as the secretion of effector molecules, which mimic certain plant regulators to facilitate the infection ^[3]. Among such effectors, there are the homologs of plant peptide hormones ^[14].

IDA homologs were identified in the two species of phytopathogenic fungi ^[15]: Melampsora larici-populina (Basidiomycota), which is the main rust pathogen of different species of Populus ^[20], and Colletotrichum fructicola (Ascomicota), a pathogen with a broad range of host plant species ^[21]. The IDA protein of M. larici-populina contains a conserved C-terminal IDA domain, but lacks an N-terminal signal domain, whereas the IDA of C. fructicola contains both predicted N-terminal signal and C-terminal functional domains ^[15].

3. Peptide Phytohormones from Plant Symbiotic and Beneficial Microbes: Si vis pacem, para bellum

The mycorrhizal fungi can modulate ethylene signaling to possess an immune-suppressive function. Thus, during plant colonization with arbuscular mycorrhizal fungus Glomus intraradice , fungal effector protein SP7 directly interacts with the pathogenesis-related Ethylene Response Factor 19 (ERF19) transcription factor, which is often induced by ethylene and fungal pathogens to overcome the ethylene-dependent plant defense system ^[22]. Other plant growth-promoting bacteria and fungi can also modulate plant defense via SA-JA antagonism or suppression of ethylene signaling. For instance, rhizosphere bacteria Rhizobacteria spp. possess ACC deaminase, an enzyme that degrades the ethylene precursor ACC and thus decreases the ethylene level in the host plant ^[23].

At the same time, in other bacterial species of Actinobacteria, Proteobacteria, and Gemmatimonadetes phyla, however, the genes encoding the possible homologs of the CLE, CEP, PSK, and PEP peptides have been identified ^[15]. Among them, Actinobacteria sp., which are considered as PGPR ^[24], encode two putative homologs of plant CLE peptides. The products of these genes lack a putative signal peptide sequence ^[15]. Interestingly, the CLE peptide motif of one of them (HBW17759.1) has high similarity with the plant nitrate-regulated CLE peptides, including the AtCLE1-7 peptides from A. thaliana and legume CLE peptides which are known as negative regulators of the symbiotic nodulation ^[25]. It is of great interest to study if the identified CLE peptide-encoding gene from Actinobacteria sp. could affect plant root growth and plant interaction with rhizobia. The hypothetical protein encoded by a single CLE gene of uncharacterized soil bacterium Gemmatimonadetes sp. (Gemmatimonadetes) is closer to the AtCLE1, AtCLE3, and AtCLE4 peptides, as well as to CLEs of cyst nematodes, and contains an N-terminal signal domain, whereas CLE of Thiotrichales sp. (Proteobacteria) is closer to AtCLE19 and AtCLE21 and lacks a signal domain ^[15].

Another example of beneficial plant–microbe interaction is plant symbiosis with arbuscular mycorrhizal fungi (AMF), which occurs in 85% of the vascular plant species ^[26]. AMF colonizes plant roots and helps the host plant to efficiently absorb minerals, especially phosphate, from the soil. The establishment of this type of symbiosis involves signaling exchange between the symbiotic partners, and AMF was shown to produce bioactive plant hormones such as cytokinin (isopentenyl adenosine) and IAA ^[27].

Various plant-interacting bacteria, fungi, and nematodes have the genes encoding the precursors of plant peptide phytohormones of CLAVATA3/EMBRYO SURROUNDING REGION-RELATED (CLE) , PLANT PEPTIDES CONTAINING SULFATED TYROSINE (PSY), phytosulphokines (PSK), C-TERMINALLY ENCODED PEPTIDES (CEP), INFLORESCENCE DEFICIENT IN ABSCISSION (IDA), RAPID ALKALINIZATION FACTOR (RALF), and PLANT ELICITOR PEPTIDES (PEP) families. All these proteins contain one or several conserved functional domains, which are essential for peptide function, and most of them also have a signal domain which is necessary for secretion, and/or variable domain. Several examples of such non-plant peptide phytohormone precursors, such as the RALF protein of Fusarium oxysporum, the CLE, CEP, and IDA proteins of plant-parasitic nematodes, and the CLE proteins of arbuscular mycorrhizal fungi, can undergo processing in plant cells to produce short mature peptides. These peptides can bind with the receptors for corresponding families of plant peptide phytohormones. In contrast, PSY-like RaxX protein of Xanthomonas oryzae pv. oryzae undergoes processing in the bacterium and binds to the specific plant receptor for RaxX, but not to the receptors of the plant PSY peptides.

4. Discussion: Strategy of Information War and “Spy Games” with Peptide Phytohormones

It is well known that some plant pathogens and beneficial plant-interacting organisms are able to use phytohormones to increase the efficiency of host plant colonization. Since phytohormones coordinate plant growth in response to environmental and developmental stimuli, pathogens with the ability to manipulate phytohormonal level and/or response could misinform the host plant about the current status of the external and internal environment, forcing it to change the developmental strategy of the plant organism. Therefore, such pathogens, in addition to the usual “race of arms”, can use the strategy of “information war” against the host plant. According to the definition of military experts, the main properties of an information war are: a flexible arsenal of weapons and high unpredictability; gradual conquest of territories; imperceptible impact on the enemy, which can be clothed in a benevolent form; lack of visible destruction, as a result of which the defense mechanisms of society are not activated. Indeed, these methods can be used by phytohormone-manipulating pathogens to invade a host plant.

Various plant pathogens and symbionts can produce effector proteins that mimic peptide phytohormones, and some of such effectors were shown to bind with plant receptors that perceive the corresponding phytohormornes of plant origin and trigger downstream signaling pathways ^{[28][29][30][31][32][33]}. In turn, plants can also use their systems of perception and signaling of peptide phytohormones to limit the colonization level by pathogens and symbionts. For example, biosynthesis of certain plant CLE peptides and activation of their receptors upon plant colonization with rhizobia form the basis of the system, named Autoregulation of Nodulation (AON), which limits the number of nodules per plant ^[34]. The CLE signaling pathways, including those participating in AON, were also shown to regulate the colonization of legume plants with arbuscular mycorrhizal fungi ^[35]. Moreover, according to our data, the AON system can be induced under the colonization of legume plants with bacterial pathogen A. tumefaciens ^[36]. Interestingly, the transcriptomic analysis of developing syncytia in soybean roots under invasion by nematode R. reniformis  revealed the upregulation of numerous genes which had previously been associated with rhizobia nodulation, such as nodule-initiating transcription factors CYCLOPS, NSP1, NSP2, and NIN, as well as multiple nodulins associated with the plant-derived peribacteroid membrane ^[37]. A possible similarity of the regulatory mechanisms underlying nodulation and development of nematode galls on roots was suggested in earlier studies that showed that plants carrying mutations in the HAR1 locus in L. japonicus ^[38] are hyper-infected by root-knot nematodes ^[39]. Thus, plants can use conserved regulatory systems, including those involving the signaling of peptide phytohormones, to interact with various pathogens and symbionts.

Finally, the hypothesis of the coevolutionary origin of non-plant peptide phytohormones gained popularity in connection with such an origin of other phytohormones of non-plant origin, such as IAA and cytokinins. The host–parasite coevolution unambiguously explains a number of colonizing strategies of various phytopathogens and plant-beneficial organisms such as the ability to influence plant growth via pathogen/symbiont-derived IAA and cytokinins. Auxins and cytokinins are evolutionally older than plants and are present in many organisms, including bacteria, amoebae, filamentous fungi, nematodes, arthropods, etc. ^[12][13]. For example, it is assumed that over 80% of the rhizosphere bacteria are able to synthesize IAA ^[27]. The evolutionally conserved function of cytokinins in a broad range of organisms consists in their role as a component of tRNA which serve mainly in improving the translation efficiency and fidelity ^[40]. At the same time, IAA produced by bacteria and fungi was considered to be a secondary metabolite resulting from a detoxification process when tryptophan starts to accumulate in the cells, and, in addition, IAA is used as a signal for gene regulation in some bacteria ^[12]. In plants and various plant-interacting organisms, IAA and cytokinins acquired more specific roles as growth regulators. Therefore, plant pathogens and symbionts, which had the enzymes involved in IAA and cytokinin biosynthesis and modifications, gained an advantage in plant colonization ^[12][13].

The origin of the genes encoding non-plant peptide phytohormones via co-evolution or HGT indicates that a molecular dialog of plants with their “enemies” and “allies” has been preceded by “spy copying of the military technologies” (in case of co-evolution) and even “theft of ready-made samples”, which might have happened directly or through bacterial intermediaries (in the case of HGT). This is not unique to plants: the acquisition of genes that facilitate interaction with the host through HGT has been observed in the pathogens of animals and other animal-interacting organisms. For example, in the genomes of necrophagous nematodes of the Pristionchus genus which feed on the remains of dead insects along with their microsymbionts, both cellulase genes from the bacterial donor, and the Diapausin genes, which encode antifungal peptides specifically produced during diapause, from insect donor, were found ^[41]. Therefore, the arms race and all sorts of spy life hacks that can be found in human society, have not been invented by humans: all these “techniques” have existed in nature for millions of years before them.