A System Biology Approach to Explore Host-Pathogen Interaction Under Phytochemical Cross Linkages

Phyto-signalling molecules are minute, but tangible that has rigorous roles in any plant-pathogen interaction. Certainly, most of the pathogen alters their biosynthesis, transport, degradation and cellular signalling responses to pave their virulence. Therefore, the gene expressions of such molecules with their correlated defense mechanisms were analysed in Arabidopsis thaliana against Erysiphe orontii (a potential biotroph), Botrytis cinerea (a potential necrotroph), Pseudomonas syringae (a bacterial hemibiotroph), and Phytophthora infestans (a fungal hemibiotroph) using molecular biology/ system biology techniques. The �ndings strongly suggested that each pathogen has its own unique infection strategy based on up-regulation and down-regulation of host phyto-signalling genes. Our studies also explored four basic pathogenic infection maps based on cross linking phyto-signalling molecules.


Abstract
Phyto-signalling molecules are minute, but tangible that has rigorous roles in any plant-pathogen interaction.Certainly, most of the pathogen alters their biosynthesis, transport, degradation and cellular signalling responses to pave their virulence.Therefore, the gene expressions of such molecules with their correlated defense mechanisms were analysed in Arabidopsis thaliana against Erysiphe orontii (a potential biotroph), Botrytis cinerea (a potential necrotroph), Pseudomonas syringae (a bacterial hemibiotroph), and Phytophthora infestans (a fungal hemibiotroph) using molecular biology/ system biology techniques.The ndings strongly suggested that each pathogen has its own unique infection strategy based on up-regulation and down-regulation of host phyto-signalling genes.Our studies also explored four basic pathogenic infection maps based on cross linking phyto-signalling molecules.

Background
Host (plant) -pathogen interaction is the multifaceted process that includes the binding of protein receptors to elicit a response by altering a wide range of host physiological aspects (1).The elicited response is manipulated by the small, but tangible molecules in host, commonly known phyto-signalling molecules (2).The phytopathogens are divided into three basic categories (biotroph, necrotroph and hemibiotroph) on the basis of their biosynthesis, transport, degradation, cell signal perception, repression and response in host plant (3).Biotroph is a plant pathogen that infects, yet fetches nutrients out of the host without killing it (4).This pathogen is adapted to cause low damage to the host, but requires high pathogenic strategic network to drive food from it (5).Due to its advanced pathogenic strategy, there is usually limited range of hosts available for it (6).Biotroph usually lacks in host cell wall degrading enzymes, but they can produce secondary metabolites, which act as virulence (7).Plant defense signalling in biotrophy involves the biosynthesis of phyto-signalling molecules and correlated expression of genes, which undergo cell death or apoptosis (8).Necrotroph is another group of plant pathogen that kills the host and then lives on it saprophytically to drive nutrients out of it (9).Necrotrophic pathogens are not specialized in their virulence as they only tend to kill their host (10).Plants resists the cell death caused by necrotrophs and detoxify their toxins by specialised defense mechanisms (11).Beside the biotrophs and necrotrophs, hemibiotroph is a class of pathogens, which rst adjust and then kill the host to drive energy out of them (12).Initially, they establish haustoria in the host tissues and then produce host degrading enzyme to destruct host tissues (13).Plant defense system against hemibiotroph is quite challenging (14).The integrated role of phyto-signalling molecules with co-expression of the genes for these pathogens is still unknown (15).In fact, the host defense response de nes the category of pathogen (16).Along with this, there is the correlated defense response initiated by the host to overcome the virulence of the pathogen (17).Among the phyto-signaling molecules, IAA appeared to be the most prevalent phyto-hormones because of variety in its biosynthetic pathways (18).These pathways need to be exploited in relation to plant-pathogen interactions.In the past few decades, this eld has been explored through mathematical and bioinformatics models to understand various facets of the interactions (19).
The aim of this study was to interlink the current understanding on the biotroph, hemibiotroph and necrotroph with the host phyto-signalling molecules with correlated co-expression of host genes to elucidate the pathogen infection strategies and host defense strategies against each class.We also intended to explore the manipulating role of phyto-signalling molecules through its biosynthesis, transport, degradation and cell signalling in host-pathogen interaction using system biology approach.In this connection, all the associated contrasting defense and virulence responses were studied to highlight the possible gaps in the eld.Therefore, we depicted four infection maps to analyse the conclusive virulence strategy of pathogen and host defense strategies.

Gene Expression Analyses of Phyto-signalling molecules
To study the effect pathogenesis on various aspects of phyto-signalling molecules, genes expressional data of their biosynthesis, transports, degradation, cell signalling perception, cell signalling repression and cell signalling response were extracted from online available browser BAR (Bio-Analytical Resource for Plant Biology) (20).Arabidopsis (Col-0) leaf tissue was inoculated through syringe in ltration method (20).BAR provided Arabidopsis eFP (Electronic Florescent Pro le) tool, to check the expression of selected signi cant genes for B. cinerea, P. syringae, P. infestans and E. orontii infection in Arabidopsis (21).The mode of inoculation was on the host leaf and the data was extracted after the host showed infection symtopms.The value obtained from expression data was in log2 ratio where negative values indicated down-regulation while positive values indicated up-regulation.Using the retrieved gene expression data, heat maps and schematic pathways were drawn revealing the strategy of each pathogen for altering various aspects of phyto-signalling molecules.

Co-expressional analyses of defensive genes
Three principle genes involved in defense responses correlated with phyto-signalling molecules were studied using Expression Angler 2016 tool with r-cut off range up to -0.23 to 0.99 (22).The data so extracted from Expression Angler 2016 tool with desired r-cut off range were subjected to yED (23) to produce co-expression networks where different colour nodes represented up-regulation and downregulation with the reference of the expressional value of principle defense gene and pathogen.Details of each gene were taken from TAIR tool (24) and a conclusive co-expression genes networks and infection maps were depicted which elucidated the infection strategy and infection level for each pathogen.

IAA biosynthesis under pathogenic attack
Expression data of IAA biosynthetic genes revealed two major IAA biosynthetic pathways in Arabidopsis, predominated by TAA1 and CYP79B3 genes.Due to the down-regulation of TAA1 under the all selected pathogens (Figure 1), it was designated as control pathway.On the other hand, expression of CYP79B3 was up-regulated under pathogenic attack hence, this pathway was referred to as pathogenic pathways (Figure 2).B. cinerea attack induced high level of CYP71A13 transcript in Arabidopsis (Figure 1a-c), modulating IAA biosynthesis pathways to enhance camalexin production on the expense of IAA (Figure 2c).By up-regulating NIT3, E. orontii and P. syringae enhanced IAA production (Figure 1d & 2a).Moreover, IAA biosynthesis was also manipulated in P. infestans infection shifting the balance toward GL biosynthesis by up-regulating expression SUR2 genes (Figure 1b & 2b).

Gene expression of defensive phyto-signalling molecules
Gene expression data of ACS2, ICS1 and LOX3 (signalling genes for ethylene, salicylic acid, jasmonic acid) with their correlated defense genes such as PDF1.2,PR-1 and VSP2 respectively, showed that LOX3 expression was high in B. cinerea infection as compared to ACS2 and ICS1.Therefore, the expression of VSP2 was high.Interestingly, the expression of PR-1 was also high despite of low expression of its correlated signalling gene.As opposed, E. orontii repressed LOX3 while expressed ICS1 and ACS2 gene.This response was accompanied by up-regulated expression of PR-1 and PDF1.2 and down-regulation of VSP2.P. infestans infection increased the expression of ACS2, followed by up-regulation of PDF1.2.Interestingly, leaves challenged with P. syringae had induced expression of ACS1 and VSP2 genes (Figure 5).

Co-expression of cross linking phyto-signalling molecules
Co-expression of high expressed VSP2 included genes encoding glycosyl hydrolase beta amylase, and cysteine lyase that can be involved in the biosynthesis of cellulose, starch and ethylene precursors.
Similarly, arginine amidohydrolase, polygalacturonase inhibiting protein, myrosinase-binding protein and phytosulfokinase were also up-regulated.Moreover, the up-regulated genes including the defense signalling genes BGL1, BAM5, and JAR2 were also the most prominent.The down-regulated genes were those coding for cysteine synthase c1, cyclic nucleotide-gated channel 12 and phosphoinositide phosphatase protein.Genes involved in ions transport such as nitrate transport, and nodulin MtN21-like transporter family were found to be down-regulated (Figure 6a).
Co-expression with upregulated PR-1 comprised genes related to chitin catabolism, glutaredoxin production, and zinc transport.Thaumatin-like protein, vacuolar sorting receptor, glutathione s-transferase production and phosphofructokinase and ADP/ATP carriers were up-regulated for cell signalling purpose.Enzymatic processes such farnesol dehydrogenase and Pumilio (APUM) proteins were also enhanced.Down-regulated genes in high PR-1 expressing Arabidopsis were found to be coding for thylakoidal ascorbate peroxidase, uracil phosphoribosyl transferase and salicylic acid-binding proteins.Some biosynthetic processes in the infection were down-regulated such as starch synthase for normal amylopectin synthesis, lysophosphatidylcholine acyltransferase (Figure 6b).
Genes co-expressed with Up-regulated PDF1.2 included hevein-like pathogenesis-related protein, cytochrome p450 for secondary metabolites and UDP-glucosyl transferase for quercetin 3-Oglucosyltransferase activity.Cell defense proteins such as Transporter k + , glutamate-cysteine ligase, and octadecanoid-responsive Arabidopsis AP2/ERF were also up-regulated.The o-mtase family 3 protein and transcription-coupled nucleotide-excision repair genes were also co-expressed.Contrary to these genes, TAT protein binding, homeobox protein and ATP synthesis coupled electron transport proteins coding genes were not expressed in Arabidopsis with induced expression of PDF1.2.The biosynthetic processes such as cellulose synthase, RNA polymerase beta' subunit-1 and trichome birefringence protein were also down-regulated (Figure 6c).

Infection Map 1st
Infection with the biotrophic pathogen, B. cinerea modulated host physiology by inducing the expression of genes involved in biosynthesis of ABA, ET, and JA and degradation of auxins, GA, BR and SA.More notably, the CKs biosynthesis and degradation genes were simultaneously repressed.Expression of genes involved in signal perception (a rst step of signalling mechanism that occurs at the cell receptor level) of GAs, CKs, ET and JA was high.Contrary to this, expression of genes responsible for auxins and SA signalling were repressed.The cell signal response (a last step of signalling mechanism, when cell produces protein) was only high for ET, JA and CKs (Figure 7a).

Infection Map 2nd
E. orontii infected leaves were characterized by enhanced expression of genes coding for GAs biosynthesis enzymes and repression of GAs degrading gene (Figure 7b).Genes involved in the biosynthesis and degradation of the rest of the phytohormones showed exact opposite trend.An exception was JA, where the biosynthesis as well as degrading genes were down-regulated.Expression of cell signal perception was very low for SA and GA, while very high for auxins, JA and ET.Interestingly, cell signalling repression to all hormones were very low, while cell signalling response was only low for auxins and SA.

Infection Map 3rd
In P. infestans exposed Arabidopsis thaliana, auxins, SA, ET, ABA, GAs and CKs biosynthesis and degradation genes were up and down regulated respectively.Interestingly, only auxins cell signalling perception genes was found to have low transcripts while those for the rest of phytohormones had high expression.where cell signalling repression of only SA and ABA was high.Moreover, cell signalling response of all were high except ABA (Figure 7c).

Infection Map 4th
Under P. syringae infection, expression of auxins biosynthesis genes was low as compared to its degradation genes.while the rest had high degradation.Genes involved in cell signal perception for all phytohormones was high except JA and ET while cell signal repression genes had high expression only for ABA and SA and high for the rest.Cell signalling response was found to be high only for GAs and CKs (Figure 7d.

IAA biosynthesis and transport varies under various pathogenic attack
The role of IAA in pathogenesis in plants already revealed that high IAA level in host promotes the advents of biotroph virulence whereas demotes the necrotroph virulence (25).Our results evaluated from gene expression of principle IAA biosynthetic gene predicted that the host increased or decreased IAA biosynthesis upon encountering a biotroph (E.orontii) or necrotroph respectively.This is evident as B. cinerea had deviated the IAA biosynthesis to camalexin production in the infected host as predicted from gene expression data, signifying the necrotroph virulence.Therefore, it can generally be assumed the total level of IAA is deviated to camalexin production under necrotroph virulence.Camalexin is a defensive secondary metabolite produced in plant during a pathogen attack (26).Similarly, up-regulated expression of genes that could re-direct the ow of IAA gravitropically from leaf to root, and from the cytosol into the mitochondria, might further minimize the level of IAA in host cell during the B. cinerea infection.Thus, IAA transport and biosynthesis were manipulated to exclude it from infection site under necrotroph virulence.However, this strategy has a potential disadvantage as camalexin can restrict the pathogen.Repression of IAA biosynthesis increases susceptibility of the host to necrotrophic fungi.This is because IAA undergoes cell pro leration and resist cell death which is opposite to necrotrophic strategy.Thus in this context, B. cinerea has diverted IAA biosynthesis to camalexin to increase its virulence.This also contributes to reduce IAA level in host, thereby accelerating cell death.BcLTF1 is a pathogen factor of B. cinerea which aids in its virulence by accelerating cell death (27).We concluded that the same factor may be involved in reducing IAA level to camalexin to accelerate cell death.
Upon encountering biotrophic E. orontii, the host IAA production is elevated as a result of up-regulated expression of NIT family genes.The pathogen also manipulated gene expression of host to impose multidirectional transport of IAA which strongly suggested that IAA level through biosynthesis and transport was high at the infection site to facilitate the (Bahari, 2018 #52) necrotroph are involved in this differential response of host.P. infestans is a fungal hemibiotroph responsible for infecting several members of solenaceae and brassicaceae including Arabidopsis (28).The genes expression pattern under P. infestans infection suggest that this pathogen also used an anomaly IAA pathway to discourage IAA biosynthesis by diverting it to GL production.Thus, it can be deduced that IAA might also toxic for hemibiotroph fungus at earlier stages of infection (such as when they are inoculated to the host plant which is speci ed at 24th hour of the treatment) (28).By contrast, bacterial hemibiotroph, P. syringae alters host auxin biology in order to promote its virulence in host (29).Analysis of the gene expression data in this regard suggested that P syringae maintained IAA biosynthesis by up-regulating NIT3 to keep IAA high at the infection site.This alteration in auxin biology in host causes two main advantages to P. syringae, IAA increases the leaking of nutrients to the apoplast and also detoxi es the antimicrobial compounds.Therefore, P. syringae like E. orontii, repressed CYP71A13 to discourage the production of camalexin in host.Interestingly, P. syringae is also known to produce its own IAA which might also be contributing to the endogenous IAA pool (30).This concludes the importance of IAA for the virulence of the bacterial pathogen.Regarding IAA transport, both followed the same strategy to increase IAA level into the infection site.
In short, the obtained conclusion from results deposed that production of IAA was not in favour of necrotrophs and fungal hemibiotrophs as IAA proliferates the infecting cell which was against the lethal strategies of fungal hemibiotroph and necrotrophs.Therefore B. cinerea and P. infestans detained the production of IAA to camalexin and GL respectively.These two group of compounds kill the infected cell, rendering it for their dinner (31).In case of biotrophs, IAA was in favour of their lethal strategy as biotrophs keep the cell alive and devour on its metabolites.Therefore E. orontii and P. syringae induced the production of IAA, keeping the cell off other secondary metabolites such camalexin and GL.

Phyto-signalling molecules are tactically manipulated under host-pathogen interactions
Each pathogen has portrayed its own manipulation over hormonal set-up of the host.Phyto-signalling molecules which also termed as phytohormones are largely involved in regulation of host-pathogen tradeoffs in contrast with growth and development (32).When model of hormonal manipulation and plant defense signalling of each class was compared with our predictions based gene expression data, some interesting facts and various gaps in the eld were discovered (Figure 8).As already discussed, IAA is considered to be toxic for necrotroph and bene cial for biotroph (33).B. cinerea (a necrotroph) has completely adopted the virulent way for auxin manipulation as it down regulated auxin biosynthesis genes and un-regulated its degradation genes accompanied by repression of genes involved in signal perception.On another hand, under E. orontii (a biotroph) infection, the host adopted defensive strategy as auxin biosynthesis was low while its degradation was high.This clearly indicated the importance of auxin biosynthesis and signalling for necrotrophic virulence rather than biotrophic virulence.
Apposing to the fact, the high auxin signal perception creates a gap despite of low cell signalling response.Our prediction regarding high auxins cell signal perception is that either E. orontii has produced auxins or auxin analogues up-regulating the transcription of perception proteins, needs to be investigated.Most of the hemi-biotrophs manipulate auxin in early stages for proliferating infection site while produce its own toxins to kill the cell in later stage for completion of its developmental stages (34).Regarding the above fact, genes involved in auxin cell signal perception for P. syringae infection was high despite of repression of its biosynthesis and up-regulation of its degradation genes.More surprisingly, in fungal hemibiotroph infection (P.infestans), we predicted high auxin degradation and cell signal response with low biosynthesis and perception.Taken together, these nding suggest that auxin cell response genes are necessary for either increasing hemi-biotroph virulence or the subsequent host defense which need to be investigated in future research.
Gibberellins were also found to have a role in plant-pathogen interaction (35).Interestingly, the host adopted gibberellins regulation for both E. orontii and B. cinerea as defensive hormone but at the same time, cell signal repression and cell signal perception of gibberellins at B. cinerea infection produced a research gap for future inspection.Our scope is that through unknown factors, B. cinerea reduced the gibberellins cell signal response to favour its necrotrophy whereas, the host decreased the gibberellins signal perception to reduce biotrophy of E. orontii.In case of hemitrophs, it was elucidated that gibberellins biosynthesis upregulation was used against P. infestans while in favour of P. syringae.Therefore, gibberellins decreased virulence of fungal hemibiotroph while increased virulence for P. syringae.Role of ABA for the host-pathogen interaction in case of our selected model pathogens produced a vast gap (36).Biosynthesis and degradation of ABA was high at the same time during B. cinerea virulence and high cellular response for E. orontii attack despite of low signalling needs to be properly investigated.Moreover, ABA shielded the host cell against P. infestans attack.However, the host cellular response was low, revealing P. syringae grip over ABA cell signalling.
Like other hormones, plant's cytokinin is also instrumental signalling molecule in host-pathogen interaction (37).Regarding biosynthesis and degradation, cytokinin increased virulence for B. cinerea where the cell signalling responses favoured host defense strategy.Interestingly, E. orontii infection opposed the strategy followed by B. cinerea as the pathogen followed cell signalling response to its favour while biosynthesis and degradation was utilized by the host defense against its virulence.P. syringae increased cytokinins degradation and at the same time the host increased its biosynthesis, indicting a pitch battle between the two.The cell signalling response in this regard was completely low which needs to investigated in wet lab.As opposed to P. syringae, P. infestans increased the cell signalling response while decreasing its biosynthesis and degradation.Salicylic acid (SA) depicted a typical system of host defense and pathogen virulence responses (38) as it favoured virulence in B. cinerea and P. infestans attack but decreased P. syringae and E. orontii attack.As opposed to SA, JA produced defense response in B. cinerea while in E. orontii attack, the host strived hard to produce an appropriate response against the virulence.In this case, the inhibition of JA biosynthesis and degradation at same time needs to be investigated under E. orontii attack.Interestingly, under P. infestans and P. syringae attack, JA favoured virulence.This determined the toxicity of JA under hemibiotroph attack on host.
B. cinerea utilized ethylene biosynthesis and signalling for its virulence whereas E. orontii used its biosynthesis and degradation for its virulence while the host utilized its signalling for defense response.It is now necessary to develop a proper understanding on the signalling defense of ethylene under E. orontii attack.Similarly, in case of hemibiotrophs, P. infestans used its ethylene biosynthesis for virulence while the signalling was utilized by the host for defense.P. syringae could not produce an appropriate virulence at level of ethylene signalling and biosynthesis.Brassinosteroids appeared to an emerging hormone in host-pathogen interaction as most of its part is clear in question.Our studied put forth few assumptions regarding BR signalling and biosynthesis as BR solely used as defensive hormone against the B. cinerea while E. orontii used it for its own virulence.Similarly, P. infestans used only its degradation for virulence while the remaining aspects needs to be investigated.More lucidly, BR was utilized by P. syringae for its virulence.

The expression of co-related defensive genes explores the strategy of the host defense
In the previous sections, it now became obvious that every plant hormone has a dual role in host pathogen interactions.Plant hormones secondarily function is to trigger various co-related defensive genes when any category of pathogen approaches in the vicinity of the plant (32).We focused on the three basic defensive molecules ethylene (ACS2), salicylic acid (ICS1), and jasmonic acid (LOX3) and their co-related defensive genes such as PDF1.2,PR-1, and VSP2 respectively in regards to host defense.Expression data of ACS2, ICS1, and LOX3 concluded that a fungal biotroph (E.orontii) upregulated the synthesis of salicylic acid at its infection.This signalling led to the expression of PR-1, but the matter of contention was the expression of PDF1.2(log2 value 2.05) during the infection despite of low expression of ACS2.This created a gap in our studies.Our perception regarding the question is the adoption of host a mechanism to eliminate the virulence by the way independent of ACS2 signalling which needed to be clari ed.PR-1 and PDF1.2 expression products are highly involved in the cell early senescence to decrease biotrophy (39).
Co-expression of PR-1 included predominate genes cadmium ion and cytokinin responsive such as CHI, and PCR2.Other gene products necessary for defense were phosphofructokinase and ADP/ATP carriers, farnesol dehydrogenase expression, 2-oxoglutarate-dependent dioxygenase and Pumilio (APUM) proteins containing PUF domain for protein transport.Production of farnesol dehydrogenase and PUM domain are not considered to have a rigorous role in host defense against a biotroph (40).Down regulated gene included thylakoidal ascorbate peroxidase, uracil phosphoribosyl transferase which degraded chloroplast.This strengthened the common perception why photosynthetic activity sustained under biotrophy.
B. cinerea had also found to have role in ethylene signalling because of the expression of its defensive gene at an intermediate level.Up-regulated expression of ACS1 and its correlated PDF1.2 genes in the presence of P. infestans indicated that infection strategy of this pathogen is different from both biotroph and necrotroph.Similarly, the high expression of ACS1 and PDF1.2under in ltrating P. syringae infection meant that ethylene signalling has signi cant role in overcoming the P. syringae virulence.
Expression of ABA responsive such as BGL1, BAM5, JAR2 was strongly correlated with the VSP2.The perception developed from key up-regulated genes during B. cinerea infection, is the encoding of glycosyl hydrolase which degraded the cellulose, hemicellulose and even neuraminidases of certain viruses, but they becomes virulent for host in case of B. cinerea (41).Similarly, Beta amylase involved in cytosolic starch catabolism; cysteine lyase for generation of precursor of ethylene biosynthesis as ethylene causes senescence, favouring pathogenesis of B. cinerea.Other encoded products of up-regulated genes are for plant own defense strategy such as arginine amidohydrolase, polygalacturonase inhibiting protein, myrosinase-binding protein and phytosulfokinase which all were ABA responsive elements.The downregulated products of genes, involving in virulence included cysteine synthase c1 for cyanide detoxi cation, cyclic nucleotide-gated channel 12 for regulation of membrane potential, and Phosphoinositide phosphatase family protein necessary for vacoular organization.Ions transport was also down-regulated to the infected leaves such as nitrate transport, and nodulin MtN21-like transporter family protein for amino import and export across the membrane which thought to be involved in cell to cell signalling during defense (42).
Previously it was reported that P. infestans is a fungal hemibiotroph, therefore, PDF1.2 co-expression was analyzed.This section further explored the role of P. infestans as incompatible pathogen due to the facts mentioned.Most of the genes co-expressed are ethylene responsive and cadmium ion as hevein-like protein, cytochrome p450 and UDP-glucosyl transferase.Transporter k+ involved in cell to cell defense system, glutamate-cysteine ligase for cell proliferation, and octadecanoid-responsive Arabidopsis AP2/ERF are all proteins for incompatible pathogen (43).The most striking defense system in case of this incompatible pathogen is methylation of cell membranes occur by o-mtase family 3 protein and transcription-coupled nucleotide-excision repair which causes any repair in DNA lesion during infection.The down-regulation of PDF1.2 showed decrease in TAT protein binding for cell surface signalling; homeobox protein having a role in leucine zinc binding; and ATP synthesis coupled electron transport.Other processes scaffold host defense were also down-regulated at the same fashion such as cellulose synthase; RNA polymerase beta' subunit-1 for transcription of many viable proteins for the host.

Conclusion
Phyto-pathogens manipulate a wide range of phyto-signaling molecules in host plants to pave way to their virulence.Through System Biology approach we found that several aspects of the host-pathogen interaction are still elusive.At the same time we found that under pathogen attack, modulation of IAA biosynthesis and transport decides fate of the combat between the defending host and attacking pathogen.Beside IAA, the pathogens also in uence correlated defense responses at the expense of the host's growth and development.Based on the available data, we suggested infection maps, which depicted the overall strategy of different groups of the pathogens to engage the host plant.

Availability of data and material
We con rm that all the data generated, and material used in this current study are available within this manuscript and its supplementary materials.Moreover, we included in-silico analyses in this study to link to our in-vitro lab experiements.The in-silico data were taken and analyzed using bioinformatics tool provided on the Bio-Analytic Resource for Plant Biology (BAR; http://bar.utoronto.ca).

Con ict of interest/competing interests
We have no competing interests to declare.

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Figure 7 Gene
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