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Title: Novel Disease Susceptibility Factors for Fungal Necrotrophic Pathogens in Arabidopsis}
Article:
Abstract:
Host cells use an intricate signaling system to respond to invasions by pathogenic microorganisms. Although several signaling components of disease resistance against necrotrophic fungal pathogens have been identified, our understanding for how molecular components and host processes contribute to plant disease susceptibility is rather sparse. Here, we identified four transcription factors( TFs) from Arabidopsis that limit pathogen spread. Arabidopsis mutants defective in any of these TFs displayed increased disease susceptibility to Botrytis cinerea and Plectosphaerella cucumerina, and a general activation of non-immune host processes that contribute to plant disease susceptibility. Transcriptome analyses revealed that the mutants share a common transcriptional signature of 77 up-regulated genes. We characterized several of the up-regulated genes that encode peptides with a secretion signal, which we named PROVIR( for provirulence) factors. Forward and reverse genetic analyses revealed that many of the PROVIRs are important for disease susceptibility of the host to fungal necrotrophs. The TFs and PROVIRs identified in our work thus represent novel genetic determinants for plant disease susceptibility to necrotrophic fungal pathogens.
Introduction:
Plants inhabit environments rich in microbial pathogens, which pose continuing threats to plant survival. However, very few pathogens are capable of successfully colonizing a specific host, suggesting the existence of efficient recognition mechanisms to activate plant defenses. In general, two types of microbial pathogens, which differ grossly in lifestyles, may be distinguished[1]. Necrotrophic pathogens use destructive and virulent strategies that promote cell death to acquire nutrients for their growth and reproduction[2, 3]. This lifestyle contrasts with that of biotrophic pathogens, which require living plant cells for growth and reproduction. Both types of pathogens elicit distinct host immune responses. Irrespective of pathogen type, the host perceives pathogens via plant pattern recognition receptors( PRRs) as pathogen-associated molecular patterns( PAMPs), and damage-associated molecular patterns( DAMPs)[4]. PAMPs are molecular tags essential for microbe viability, which are conserved between diverse genera, and are an efficient form of pathogen monitoring in plants. DAMPs are plant-generated signals in response to pathogen damage. PAMP recognition by PRRs triggers basal defense responses, known as pattern-triggered immunity( PTI). PTI provides protection against non-host pathogens, and limits disease caused by virulent pathogens[5]. The timing and efficiency in activating various basal defense mechanisms is thought to underlie differences in host susceptibility to necrotrophic pathogens. Our understanding of PAMP-triggered necrotrophic immunity is largely derived from Botrytis cinerea; one of the most important fungal plant pathogens[2, 3]. This species exhibits a broad geographic range and has the capacity to cause severe damage on plants, resulting in large economic losses in agriculture[6]. The fungal cell wall component chitin, and its constituent oligosaccharides, are fungal PAMPs, which activate numerous defense responses. Polygalacturonase( PG) is another fungal component essential for virulence. This protein is detected, independently of its enzymatic activity, by the plant as a PAMP and activates host defense responses[7]. Moreover, PGs can act on the host cell wall to degrade pectin, which is the primary carbon source for the pathogen, to produce oligogalacturonides( OGs). OGs of a certain length( 10 to 15 degrees of polymerization) are, in turn, enriched by the activation of a plant encoded PG-inhibiting protein. These OGs may function as DAMPs that activate plant immunity[8]. A plant cell wall-associated kinase( WAK1) functions as a receptor for the immunoactive OGs[9]. In addition, intracellular mitogen-activated protein( MAP) kinase activity[10], and the CERK1 interacting receptor-like kinase( BIK1), appear essential to drive chitin induced PTI[11–13]. Resistance and susceptibility to necrotrophs is a genetically complex process and comprise the coordinated action of a wide range of hormones, including ethylene( ET), jasmonic acid( JA), salicylic acid( SA), and abcisic acid( ABA)[14–17]. In addition, secondary metabolites, including the phytoalexin camalexin, and other metabolites derived from tryptophan metabolism( e. g., indolglucosinolates), contribute to necrotroph resistance[18–20]. Resistance to necrotrophs is also determined by plant cell wall composition; mutants with defects in primary( e. g., cev1 mutant) and secondary( e. g., irx mutants) wall cellulose synthase( CESA) expression or function showed increased resistance to necrotrophic fungi[21–24]. Coordinated and timely regulation of genes in immune response pathways is central to effective plant defense[25]. Different transcription factors( TFs) that affect immune responses towards necrotrophic fungal pathogens have been described: WRKY33 controls camalexin biosynthesis and is a major immune response regulator against necrotrophic fungi[26, 27]; the MYB-related BOS1 restricts necrosis[28]; ASYMMETRIC LEAVES( AS1) regulates JA-related genes, which affects resistance against B. cinerea[29]; MYB51 is associated with the activation of indole glucosinolate biosynthetic genes[30]; the basic helix-loop-helix leucine zipper TF MYC2 regulates necrotroph resistance by modulating JA responses via an intermediate TF tier[31], a process antagonized by the ERF-type TF ERF1; the homeodomain OCP3, initially identified as a plant immunity repressor to necrotrophs[32], was recently shown to function as a regulator of an editing control mechanism of plastidial mRNAs[33]; and MYB46, which suppresses B. cinerea resistance by the regulation of genes encoding cell wall proteins and enzymes[23]. Interestingly, the enhanced disease resistance to B. cinerea in the myb46 mutant was associated with an early down-regulation of CESA genes following fungal infection[34]. In summary, these results reinforce the hypothesis that a cell wall integrity surveillance system evolved to sense the presence of a pathogen, and to transduce signals into a rapid transcriptional reprogramming of the affected cell. This transcriptional reprogramming might serve to promote fungal growth or, alternatively, activate plant immunity, to facilitate susceptibility or resistance, respectively. The balance between these two responses might determine the degree of disease. Although several molecular components that affect resistance or susceptibility against fungal necrotrophs have been characterized, identification of plant disease susceptibility factors that aid pathogens in gaining access to the host plant cell, or that facilitate fungal growth, remains limited. Here, we identify and characterize four TFs that are important for disease resistance towards two fungal necrotrophs, i. e. Botrytis cinerea and Plectosphaerella cucumerina. We subsequently identified a set of 77 genes that were commonly up-regulated in the four TF mutants. Many of these genes encode peptides that contain secretion signals that we tentatively have named PROVIR factors. We show that many of the PROVIR factors also function in disease susceptibility to fungal necrotrophic pathogens. Finally, in vivo localization studies revealed common pericellular localization of the PROVIR factors.
Discussion:
Disease susceptibility caused by infectious pathogens affects most plants in their natural environment, and plants combat the majority of intruders by activation of elaborate immune responses, which typically results in an effective disease resistance response. Nevertheless, in many cases, pathogen adaptation provides a bypass to a plant’s defense and susceptibility to attackers appears. However, other molecular mechanisms serve as a foundation for immune-response independent processes in plant cells, which allow further ingress of the invading pathogen, and contribute to plant susceptibility to pathogens[60]. In this study, we identified TFs that are co-regulated with MYB46 and CESA4, 7, and 8, that are involved in disease susceptibility to fungal necrotrophs[21, 24]. Our rationale was that genes co-regulated with MYB46 and CESA4/7/8 may be involved in related biological processes and therefore also regulate critical aspects of disease resistance/susceptibility to necrotrophs. We found that several TFs, in particular ZFP2, BHLH99, PAP2, and AT1G66810, are required for plant resistance to fungal necrotrophs. Arabidopsis mutants defective in any of these four TFs showed remarkable disease susceptibility to B. cinerea and P. cucumerina. Interestingly, the disease susceptibility of the four mutants was not due to defects in immune signaling, since JA- and SA-responsive genes, which are the two main defense-signaling pathways in Arabidopsis, were not compromised. Callose deposition, thought to function as the first-line defense barrier to these fungal pathogens[17], was also not compromised in the mutants. These observations indicate that other host processes that contribute to plant disease susceptibility were activated in the mutants. The identified TFs might somehow be part of a “late damage control” machinery of the plant rather than the “detect and destroy” mechanism that traditionally marks the front-line immune systems. Whole genome transcriptome analysis of Col-0, zfp2, bhlh99, pap2 and at1g66810 insertion mutant plants revealed that the four mutants shared 77 up-regulated genes. A substantial proportion of these genes encoded secreted peptides, which might act as local signals( peptide hormones) mediating cell-to-cell communication reported to function in the plant-specific paracrine/autocrine system[42, 52, 53]. These results also indicate that the four TFs redundantly activate similar signal molecules and/or pathways to fulfill related cellular purposes. Peptide receptors are typically part of the receptor-like kinase( RLK) protein family, which may recognize different types of signaling peptides. Several of these receptors are leucine rich repeat( LRR)-RLKs or receptor-like proteins( LRR-RLPs), which can oligomerize upon peptide binding, and subsequently relay messages via phosphorylation cascades[61]. The expression of the signaling peptide family members was induced in Col-0 plants following P. cucumerina inoculation, and over-expression of the signaling peptides led to enhanced P. cucumerina susceptibility. We speculate that the production and recognition of specific ligand peptides might elicit signaling processes that offer certain fungal advantages, either by improving the recognition of, or the attachment to, the host, or simply by improving the development of the pathogen, which could contribute to the enhanced susceptibility. Thus, some pathogen species might have adapted to these plant processes to improve the invasion of the host. These non-immune related processes in the plant, therefore, contribute to the susceptibility to pathogens. In addition to the signaling peptides, we further characterized thirteen genes from the common transcriptional signatures of the hyper-susceptible zfp2, bhlh99, pap2 and at1g66810 mutants. These genes encode proteins of unknown function, and were here coined as PROVIR1 to 13. Over-expression of many of the PROVIR factors in Arabidopsis conferred increased susceptibility to the necrotroph P. cucumerina, and, conversely, loss-of-function mutants conferred increased resistance. These observations indicate that most PROVIR factors were important for fungal pathogenesis. Although the functions of the PROVIR proteins remain to be elucidated, the common PROVIR association with the PM/apoplast, suggest that the PROVIR polypeptides may work in signaling processes via membrane receptors, or perhaps as scaffolding proteins in larger protein complexes as they are lacking clear GPI-anchoring and transmembrane domains. However, post-translational modification, such as palmitoylation cannot be excluded. Palmitoylation alone is typically not sufficient to anchor proteins to the PM, but might serve as an auxiliary system. Moreover, PROVIR factors were easily solubilized with neutral extraction buffers lacking detergents, suggesting that their membrane association is weak, presumably through protein-protein or ionic interactions. Understanding the mechanism of how PROVIR proteins specifically localize to membranes is, however, a challenge for future research. Nevertheless, the PROVIR localization resembles other membrane-associated proteins of unknown function, which were recently described as remorin proteins during microbe and plant symbiosis[62]. Our findings provide a novel principle of plant host disease susceptibility to fungal necrotrophs; a process where knowledge is limited when compared with the large number of molecules and proteins identified to mediate susceptibility to biotrophic and hemibiotrophic plant pathogens[60]. Characterization of the remaining factors of the common 77 member that showed transcriptional changes in the TF mutants, as well as deeper functional characterization of the PROVIR1-13 factors and the additional signaling peptides identified here, should allow us to uncover molecular processes that underlie immune-response independent aspects of plant disease susceptibility. This course of study can provide new ways to develop strategies in breeding programs aimed at increasing crop disease resistance.
Diseases caused by pathogens affect most plants in their natural environment . Plants combat the majority of these intruders by activating elaborate immune responses , which typically result in a disease resistance response . Nevertheless , pathogens have typically evolved ways to bypass plant defenses , and susceptibility to pathogens re-appears . In addition to this occasional immune failure of the host , other immune-response independent processes allow further ingress of the invading pathogen , and contribute to plant pathogen susceptibility . We identified four transcription factors ( TFs ) that are required for effective disease resistance to fungal necrotrophs . These TFs regulate critical aspects of disease resistance/susceptibility to necrotrophs without interfering with immune signaling . Mutant plants defective in any of these four TFs commonly induce about 80 genes , with a substantial proportion encoding peptides with secretion signals that are described to act as local signals ( peptide hormones ) during cell-to-cell communication , and that function in the plant-specific paracrine/autocrine system . We further show that many of these peptide hormones affect disease susceptibility of the host to necrotrophs . Our findings have thus uncovered many new factors that underpin immune-response independent processes of plant disease susceptibility .