Genetic and Molecular Basis of Plant Resistance to Pathogens PDF

JGG Available online at www.sciencedirect.com Journal of Genetics and Genomics 40 (2013) 23e35...

JGG Available online at www.sciencedirect.com Journal of Genetics and Genomics 40 (2013) 23e35 REVIEW The Genetic and Molecular Basis of Plant Resistance to Pathogens Yan Zhang a, Thomas Lubberstedt b, Mingliang Xu a,* a National Maize Improvement Center of China, China Agricultural University, Beijing 100193, China b Iowa State University, Department of Agronomy, 1204 Agronomy Hall, Ames, IA 50011, USA Received 5 November 2012; revised 29 November 2012; accepted 3 December 2012 Available online 10 December 2012 ABSTRACT Plant pathogens have evolved numerous strategies to obtain nutritive materials from their host, and plants in turn have evolved the preformed physical and chemical barriers as well as sophisticated two-tiered immune system to combat pathogen attacks. Genetically, plant resistance to pathogens can be divided into qualitative and quantitative disease resistance, conditioned by major gene(s) and multiple genes with minor effects, respectively. Qualitative disease resistance has been mostly detected in plant defense against biotrophic pathogens, whereas quantitative disease resistance is involved in defense response to all plant pathogens, from biotrophs, hemibiotrophs to necrotrophs. Plant resistance is achieved through interception of pathogen-derived effectors and elicitation of defense response. In recent years, great progress has been made related to the molecular basis underlying hostepathogen interactions. In this review, we would like to provide an update on genetic and molecular aspects of plant resistance to pathogens. KEYWORDS: Resistance to pathogen; Innate immune system; R genes INTRODUCTION antimicrobial compounds. Once pathogens penetrate the cell wall, the plant two-tiered innate immune system is activated to Plants are in a continuous evolutionary battle against counter-attack pathogen invasion. The first tier of plant a multitude of microbial and other pathogens. Pathogens immune system is PAMP-triggered immunity (PTI), which is usually access the plant interior either by penetrating the leaf based on the sensitive perception of pathogen- or microbe- and root surfaces directly or by entering through wounds and associated molecular patterns (PAMPs or MAMPs), and the natural openings such as leaf stomata. During the invasion second tier is effector-triggered immunity (ETI), which process, plant pathogens degrade the cell wall by synthesizing perceives effectors produced by pathogens that have evaded and liberating cell wall-degrading enzymes, then deliver PTI (Jones and Dangl, 2006). pathogen effectors by specialized infection structures, and In this review, the genetic and molecular aspects of plant eventually interfere with the normal activities of the host resistance will be discussed, including the genetic basis for (Pajerowska-Mukhtar and Dong, 2009; Tilsner and Oparka, plant resistance, signaling pathways, perception of pathogens 2010; Horbach et al., 2011). Plants in turn have evolved and defense mechanisms of plants. sophisticated defense mechanisms to combat pathogen inva- sion by blocking pathogen entrance and activating a range of GENETIC BASIS OF PLANT DISEASE RESISTANCE defense responses. The first barriers that pathogens face are the waxy cuticular layers and cell wall as well as preformed Qualitative and quantitative disease resistance * Corresponding author. Tel: þ86 10 6273 3166, fax: þ86 10 6273 3808. Plant disease resistance is generally divided into qualitative E-mail address: [email protected] (M. Xu). and quantitative resistance. The former is controlled by major 1673-8527/$ - see front matter Copyright Ó 2013, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved. http://dx.doi.org/10.1016/j.jgg.2012.11.003 24 Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 R gene(s), and the latter is conditioned by multiple genes with Arabidopsis, which has a C-terminal extension with a putative minor effects (Poland et al., 2009). nuclear localization signal (NLS) and a WRKY domain R gene usually confers complete resistance to a specific (Deslandes et al., 2002). The seventh class encodes enzymatic pathogen or pathogen race and is easy to manipulate for basic proteins which contain neither a LRR nor NBS domain. For research and crop improvement. Many R genes have been example, the maize Hm1 gene that provides protection against cloned, and the downstream responses triggered by R genes corn leaf blight caused by the fungal pathogen Cochliobolus are becoming increasingly well understood. As the resistance carbonum encodes an enzyme, HC toxin reductase, which mediated by major R genes can be rapidly overcome by new detoxifies a specific cyclic tetrapeptide toxin produced by the virulent pathogens, R genes represent a frustrating battle in fungus (Johal and Briggs, 1992). disease control for plant breeders and farmers. In addition to the above mentioned classification for Quantitative disease resistance (QDR) is controlled by mostly dominant resistance genes, several recessive resis- multiple genes, each contributing to partial resistance. QDR tance genes have been identified in plants. For example, two leads to lower selection pressure against pathogen variants, recessive genes, bs5 and bs6, which control resistance to all and those that overcome an individual quantitative resistance known races of Xanthomonas euvesicatoria in peppers, have locus (QRL) have little advantage. Thus, quantitative disease been characterized (Vallejos et al., 2010). In rice, a novel resistance tends to be more durable than R gene-mediated recessive resistance gene, xa34, was mapped to a 204-kb resistance (Parlevliet, 2002). Many studies on quantitative interval and confers resistance against Xanthomonas oryzae disease resistance have indicated its importance in crop pv. oryzae (Zhu et al., 2011). A question for recessive disease improvement, and variation in quantitative disease resistance genes is whether they are really resistance genes resistance can be exploited by traditional or marker-aided or are simply mutant forms of susceptibility alleles? If plant breeding methods, leading to a commercially accept- susceptibility is an active process in which a host gene is able level of disease control. targeted by a pathogen protein to induce susceptibility, then the recessive resistance may be a passive process due to lack Major genes for disease resistance of susceptibility instead of activation of defense responses. Though investigations of recessive resistance genes are still In the last two decades, numerous R genes for qualitative in the early stages, the current available evidence favor the resistance have been cloned from many plant species, and they hypothesis that the recessive resistance is a passive process. can be generally divided into seven classes based on their amino For instance, the resistance mediated by a recessive rice acid motif organization and membrane-spanning domains xa13 gene can be overcome by the disease susceptibility (Gururani et al., 2012). The largest class consists of NBS-LRR gene Os11-N3 (Yang et al., 2010). Several evidence sug- genes, which contain a nucleotide-binding site (NBS) and gested that xa13 has atypical R gene responses, which a leucine-rich repeat (LRR) domain (Young, 2000). NBS-LRR indicates that Xa13 may act as susceptibility allele and xa13 genes in plants are typically divided into two groups according is the mutant form (Iyer-Pascuzzi and McCouch, 2007). The to their N-terminal domains: one is the TIR group genes that are pvr2 locus in pepper corresponds to an eukaryotic initiation composed of an N-terminal domain having homology to the factor 4E (eIF4E ) gene, conferring recessive resistance intracellular domain of the Drosophila Toll and mammalian against strains of potato virus Y (PVY) (Ruffel et al., 2002). interleukin-1 receptors, and the other group of genes code for The novel function for eIF4E supports virus (Potyvirus, pea the CC (coiled-coil) domain (Gururani et al., 2012). There are seed-borne mosaic virus) movement from cell-to-cell, in about 200 genes that encode proteins with similarity to the addition to its probable support for viral RNA translation nucleotide-binding site and other domains characteristic of (Gao et al., 2004). The interaction between the Potyvirus plant resistance proteins in Arabidopsis, in which 149 are NBS- genome-linked protein (VPg) and eIF4E is important for LRR proteins (Meyers et al., 2003). The second class is char- virus infectivity; and the recessive resistance results from acterized by extra-cytoplasmic LRRs and a C-terminal incompatibility between the VPg and eIF4E in the resistant membrane anchor, represented by the tomato Cf genes (Jones, genotype (Ruffel et al., 2002). 2001). The rice Xa21 gene, which confers resistance to a bacterial pathogen, is characteristic for the third class of R Quantitative loci for disease resistance genes, as it features both extracellular LRRs and a trans- membrane protein kinase (Song et al., 1995). The Arabidopsis Quantitative resistance loci (QRL) may be involved in RPW8 protein is an example of the fourth class of resistance a wide range of biological activities in plants, including 1) gene encoding proteins, which contains a membrane protein regulating morphological phenotypes and developmental domain and a putative coiled-coil domain (CC) (Wang et al., process, 2) promoting basal defense, 3) encoding enzymes to 2009; Gururani et al., 2012). The fifth class of resistance gene detoxify pathogen-produced phytotoxins, 4) assisting with encoding protein contains putative extracellular LRRs, a PEST defense signal transduction, 5) circadian clock-associated (Pro-Glu-Ser-Thr) domain and short motifs that might target the genes, and 6) weaker alleles of R genes or a unique set of protein for receptor-mediated endocytosis. This class is repre- previously unidentified genes. sented by the Ve1 and Ve2 genes in tomato (Kawchuk et al., Flowering time is closely correlated with resistance to 2001). The sixth class is represented by the RRS1-R gene in many pathogens, as susceptibility is enhanced after  Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 25 flowering, indicating that QRL may be genes that regulate MECHANISMS UNDERLYING PLANT RESISTANCE flowering time (Collins et al., 1999). PAMP-triggered TO PATHOGENS immunity, a form of basal defense, confers resistance to broad-spectrum pathogens in plants. In this case, QRL Biotrophic and necrotrophic pathogens represent mutants or different alleles of genes involved in basal defense (Dunning et al., 2007). The level of camalexin Plant pathogens are broadly divided into biotrophs and is correlated with quantitative disease resistance based on necrotrophs, according to their lifestyles. Biotrophic patho- a biochemical study of the ArabidopsiseBotrytis pathos- gens gain nutrients from living host tissue, whereas ystem, and camalexin sensitivity of different pathogen necrotrophic pathogens kill host tissue and feed on the isolates contributes to isolate specificity (Denby et al., 2004; remains. There are, however, many hemi-biotrophic pathogens Kliebenstein et al., 2005; Schlaeppi et al., 2010), indicating that behave as both biotrophs and necrotrophs, depending on that QRL may be related to the production of anti-pathogen the conditions or the stages of their life cycles. Many fungi chemicals. Activation of the salicylic acid (SA)-dependent that are commonly considered necrotrophs but have a bio- signaling pathway can lead to expression of certain trophic stage early in their infection process, and may thus be pathogenesis-related proteins that contribute resistance to better described as hemibiotrophs (Pieterse et al., 2009). The biotrophs. Likewise, activation of the jasmonic acid (JA)- and molecular mechanisms underlying activation of plant defense ethylene-dependent signaling pathways strengthens plant responses are quite different between biotrophs and defense responses to necrotrophs (Thomma et al., 1998; necrotrophs. Pieterse et al., 2009). Moreover, SA, JA, and ethylene signaling pathways interact extensively with one another Plant resistance to biotrophs (Koornneef and Pieterse, 2008; Robert-Seilaniantz et al., 2011). There are many examples of signaling components Previous studies suggest that plant defense against bio- that regulate variable levels of susceptibility when mutated trophic pathogens is largely due to gene-to-gene resistance (Koornneef and Pieterse, 2008). Therefore, different alleles (Glazebrook, 2005) (Fig. 1). R gene-mediated resistance of the genes involved in the regulation of these signaling usually results in hypersensitive response (HR), which is pathways are speculated to be QRL (Poland et al., 2009). thought to be very important for plants to combat biotrophic Recently, some novel genes involved in R gene-mediated pathogens, such as Peronospora parasitica, Pseudomonas resistance against downy mildew were identified in Arabi- syringae, and Erysiphe spp., by restricting their access to dopsis and they were controlled by the circadian regulator, water and nutrients (Glazebrook et al., 1997; Aarts et al., CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1). In addi- 1998; Feys et al., 2001). R gene-mediated resistance also tion, an interconnection between R gene-mediated pro- activates SA-dependent signaling, leading to an activation of grammed cell death (PCD) and basal resistance was also a string of presumed defense effector genes. This activation of established, as an alteration in the former was also affecting SA signaling occurs throughout the plant to develop systemic the latter (Wang et al., 2011b). There are reports of quanti- acquired resistance (SAR) against subsequent pathogen tative disease resistance that is controlled by non-classical infections (Glazebrook, 2005). During SAR, deposition of resistance genes. For instance, pi34, which shows partial callose and lignin occurs in the plant cell walls, and plants resistance to rice blast, is located in a 65.3-kb interval, acquire the ability to mount a rapid HR. Analysis of Arabi- spanning 10 open reading frames and none of the candidate dopsis mutants with defects in various defense-related genes have sequence similarity to any previously reported signaling pathways provides support for the idea that SA defense genes (Zenbayashi-Sawata et al., 2007). signaling can result in resistance to biotrophic pathogens. For To date, only a few QRL conferring QDR have been cloned instance, both EDS1 and PAD4 play important roles in SA and characterized. In rice, some QRL represent genes that signaling, and mutations in these two loci weaken resistance to have not been previously reported to function in disease some P. parasitica isolates. The NPR1 (Nonexpressor of resistance, such as the pi21 gene for rice blast, which encodes pathogenesis-related genes 1) gene is a master regulator for a mutated proline-rich protein and has no similarity to SA signaling. The npr1 mutant is more susceptible to a variety currently known defense-related genes (Fukuoka et al., 2009). of pathogens (Cao et al., 1994; Bi et al., 2011). Mutants with In wheat, Yr36 confers resistance to a broad spectrum of stripe defective SA synthesis, including eds5 (Nawrath and Metraux, rust races under high temperatures (25 C35 C) in adult 1999) and sid2 (Nawrath and Metraux, 1999) show enhanced plants, and encodes both kinase and putative START susceptibility to P. syringae as well. Two plant-specific DNA- (steroidogenic acute regulatory protein-related lipid transfer) binding proteins, SAR Deficient 1 (SARD1) and CBP60g, are lipid binding domains, which were essential to confer resis- key regulators for SA synthesis. Knocking out SARD1 tance (Fu et al., 2009). Lr34 confers resistance to slow rust, compromises basal resistance and SAR. In the sard1-1/ leaf rust, and powdery mildew in wheat and has been used for cbp60g-1 double mutant, pathogen-induced SA synthesis are over 50 years in breeding. The protein encoded by Lr34 is blocked in both local and systemic leaves, resulting in a putative adenosine triphosphate-binding cassette (ABC) compromised basal resistance and loss of SAR (Zhang et al., transporter of the pleiotropic drug resistance subfamily 2010c). In addition, the expression of CBP60g/SARD1- (Krattinger et al., 2009). dependent resistance-related genes are modulated by 26 Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 Fig. 1. Molecular basis of plant resistance to pathogens. The upper part of the diagram is the defense response to necrotrophic pathogens, conferred by RLKs, defensin, phytoalexin, and JA/ET signaling. The lower part of the diagram is the two-tiered immune system of plant resistance to biotrophic pathogens. The first tier of defense (PTI) is triggered on perception of P/DAMPs by membrane-anchored PRRs, followed by activation of MAPK cascade and downstream transcription factors, leading to immune responses. The second tier of defense is elicited by pathogen effector via an interaction with R protein (ETI), in which the interaction between R protein and pathogen effector oscillates between compatible and incompatible reactions over time. The R gene-mediated resistance to biotrophic pathogens usually results in hypersensitive response (HR), and meanwhile activates SA-dependent signaling, leading to systemic acquired resistance (SAR). Abbreviations: HSTs, host-selective toxins; PRRs, pattern recognition receptors; TTSS, type III secretion system; ROS, reactive oxygen species; HR, hypersensitive response; P/DAMPs, pathogen/damage-associated molecular patterns. CBP60g/SARD1, suggesting that CBP60g and SARD1 affect recognition receptors (PRRs) are involved in the perception of defense responses in addition to SA production (Wang et al., necrotrophic fungi, such as receptor-like protein kinases 2011a). (RLKs) (Llorente et al., 2005; Berrocal-Lobo and Molina, 2008) (Fig. 1). One of the putative RLKs is encoded by Plant resistance to necrotrophs BIK1 (Botrytis-induced kinase 1) gene, which is predicted to be involved in early stages of plant defense against B. cinerea Generally it was assumed that no gene-for-gene resistance and A. brassicicola (Veronese et al., 2006). Host-selective functions in resistance to necrotrophic pathogens, but it was toxins (HSTs) are considered as efficient weaponry of indicated in a number of reports that several plant pattern necrotrophic fungi and the diseases caused by necrotrophs are  Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 27 manifested by the appearance of necrotic lesions (Ciuffetti and HR is associated with increased resistance against bio- Tuori, 1999; van Kan, 2006). For instance, tan necrosis caused trophs but decreased resistance to necrotrophs. HR does not by the fungus Pyrenophora tritici-repentis results from the protect Arabidopsis against infection by B. cinerea, which is action of the HST toxin, Ptr ToxA (Ciuffetti and Tuori, 1999). the necrotrophic pathogen that attacks more than 200 plant Exogenous application of the phytotoxin botrydial causes species including many crops (Kliebenstein and Rowe, 2008). severe chlorosis and collapse in plant tissue to facilitate The high level of HR activated in biotroph-plant pathosystems penetration and colonization of fungal Botrytis cinerea may also provide an entry for necrotrophs in the local (Colmenares et al., 2002). Phytoalexins are low-molecular- environment. weight antimicrobial compounds produced in response to pathogen infection or treatments with various abiotic elicitors. RNA silencing in plant resistance One of them, phytoalexin camalexin, is an indole derivative produced by Arabidopsis in response to infection by the A primary means by which plant defend against viral bacterial pathogen P. syringae (Fig. 1). The pad3 mutation, infection is RNA silencing (Dinesh-Kumar, 2009), which is which inhibits camalexin production, has no negative effect on triggered by double-stranded RNA. The RNA sequence that is resistance to the biotrophic pathogen P. syringae, but does lead homologous to the dsRNA is degraded and the gene that to decreased resistance to the necrotrophic fungal pathogen A. encodes the RNA is effectively silenced (Meister and Tuschl, brassicicola (Thomma et al., 1999a; Zhou et al., 1999). This 2004). It was reported that most plant viruses are RNA viruses. clearly demonstrates that camalexin plays an important role in The RNA silencing process is composed of the dsRNA trigger, Arabidopsis resistance to necrotrophs (Chassot et al., 2008). the processor Dicer or a Dicer-like (DCL) protein, small RNAs Camalexin was later shown to enhance the resistance against (siRNAs or miRNAs) of 21e24 nt in length and the effector two other necrotrophic pathogens, B. cinerea and L. maculans complex RISC in which the Argonaute (AGO) protein is the (Bohman et al., 2004). In plants, a group of small cysteine-rich key player. Viruses encode RNA-dependent RNA polymerases proteins, known as defensins, displays antimicrobial activities (RdRPs) and produce the opposite-sense of the viral genome against micrographic fungi, which is considered an active in the first step of replication, thus generating many long participant in the plant innate immunity by triggering fungal dsRNA species that trigger RNA silencing (Waterhouse et al., membrane permeabilization and reducing hyphal elongation 1998; Dalmay et al., 2000;). It was also suggested that viral (Aerts et al., 2007) (Fig. 1). A pathogenesis-related gene RNA secondary structures might be the trigger of RNA PDF1.2, encoding defensin in Arabidopsis, was regulated by silencing (Vance and Vaucheret, 2001). In plants, there are JA. It was reported that plants decreased in JA signaling several homologues of the DICER endonuclease, and these exhibit a low level of PDF1.2 expression during fungal DCL enzymes generate siRNA (short interfering RNA) in an infection and show enhanced susceptibility (Mengiste et al., antiviral response (Xie et al., 2004). Virus-induced gene 2003; Veronese et al., 2004). silencing (VIGS) functions as a natural antiviral defense JA- and ethylene-mediated defense responses are expected mechanism, in which host RNA silencing machinery targets to play key roles in resistance to necrotrophic pathogens (Xie and processes the virus derived dsRNA into vsiRNAs (virus- et al., 1998; Thomma et al., 1998; Thomma et al., 1999a) derived siRNAs) that are then recruited to host RISC (Fig. 1). As known, JA activity in Arabidopsis requires the complexes, which target and inhibit gene expression and function of COI1 (Xie et al., 1998; Pre et al., 2008). Plants protein translation in the viral genome. Viral effectors could with mutations in coi1 show enhanced susceptibility to suppress the host RNA silencing responses. Such suppressors infection by the fungal pathogen B. cinerea, indicating that have been identified in many plant viruses (Dinesh-Kumar, JA signaling is required for resistance to necrotrophs 2009). These studies indicate that the different suppressors (Thomma et al., 1998). In Arabidopsis, the ethylene- interfere with the host-silencing machinery, and many viruses insensitive ein2-1 mutants are more susceptible than wild- independently developed means to suppress RNA silencing. type plants to infection by two different strains of B. cinerea (Thomma et al., 1999a). Inoculation of wild-type A TWO-TIERED INNATE IMMUNE SYSTEM Arabidopsis plants with the fungus Alternaria brassicicola IN PLANTS results in an activation of three resistance genes, and these genes fail to function in the ein2-1 mutant (Thomma et al., Plants lack mobile defender cells and a somatic adaptive 1999a). Furthermore, the A. brassicicola and B. cinerea immune system. Instead, they have evolved an innate immune necrotrophs are restricted by JA- or ethylene-dependent system that efficiently detects potentially dangerous microbes defense responses (Thomma et al., 1999b; Ferrari et al., and then counter-attacks their invasion. There are two tiers in 2003; Bohman et al., 2004). These findings support the idea the plant immune system. The first tier is based on the that JA- and ethylene-controlled responses play vital roles in sensitive perception of PAMPs (or MAMPs) through PRRs on Arabidopsis resistance to necrotrophic pathogens. In addition, the cell surface of the plant. Immune responses to PAMPs are treatment of pad3 plants with exogenous JA reduces the categorized as PTI. Successful pathogens have evolved to susceptibility to infection by Botrytis cinerea (Thomma et al., produce effectors to inhibit PTI, and plants can perceive such 1998), further supporting the idea that JA signaling is effectors through additional receptors (R proteins) to form the required for resistance. second tier of defense, ETI. There is a dynamic co-evolution 28 Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 between plants and pathogens, and this dynamic process heptaglucoside, that are present in the cell wall of the oomy- continues, as some pathogens have acquired effectors that cete Phytophthora sojae during contact (Fliegmann et al., interfere with ETI (Jones and Dangl, 2006). 2004; Zipfel, 2009). However, the signaling pathway after perception is unclear. A semidominant Arabidopsis mutant, PTI snc2-1D, constitutively activates defense responses. A suppressor screen of snc2-1D revealed that mutations in As the first tier of the plant resistance system, PTI is trig- WRKY70 suppress the constitutive defense responses in snc2- gered by PAMPs. Although numerous PAMPs have been 1D. Since WRKY70 may have a role in the regulation of described, only a few pattern recognition receptors (PRRs) conversion of SA to salicylic acid glucoside (SAG), this have been identified so far (Zipfel, 2009) (Fig. 1). A typical suggests that WRKY70 functions in an SA-independent example is the leucine-rich repeat-receptor-like protein kinase pathway downstream of snc2-1D (Zhang et al., 2010d). (LRR-RLK), named FLS2, which is located in the plasma Other receptor-like proteins were identified in tomato and membrane to bind a bacterial flagellin that contains a 22- Arabidopsis, but their detailed interactions and signaling amino acid epitope (flg22) (Gomez-Gomez and Boller, 2000). mechanisms are unknown (Ferrari et al., 2007; Schwessinger FLS2 initiates immune signaling by association with another and Zipfel, 2008). In addition to PAMPs, plant cells can leucine-rich repeat-receptor-like kinase, BAK1. A receptor- recognize molecules from damaged host cells upon microbial like cytoplasmic kinase BIK1 is rapidly phosphorylated attack, which are referred to as damage-associated molecular upon flagellin perception by both FLS2 and BAK1. Phos- patterns (DAMPs) (Lotze et al., 2007; Qutob et al., 2006a). For phorylated BIK1 then transphosphorylates FLS2/BAK1 to example, plants can recognize oligo-a-galacturonides released propagate flagellin signaling (Lu et al., 2010). The mitogen from damaged cell walls by fungal hydrolytic enzymes and activated protein kinases (MAPKs) are involved in various Nep1-like (necrosis and ethylene-inducing peptide1-like) processes in plants, including plant immunity (Asai et al., proteins secreted by many pathogens (Nurnberger et al., 2004). 2002). A complete MAPK cascade and downstream tran- Recognition of PAMPs is associated with a series of scription factors are then activated after flg22 detection, which responses to prevent microbial growth (Nicaise et al., 2009). activates the defense response (Nicaise et al., 2009). FLS2 was The first physiological response to PAMP recognition in plant reported to activate two MAPK cascades. One consists of an cells is alkalinization of the growth medium (Garcia-Brugger MEKK-MKK4/5-MPK3/6 complex and acts positively on et al., 2006). There are fluxes of Hþ, Kþ, Cl, and Ca2þ PTI, while the other consists of MEKK1-MKK1/2-MPK4 and after PAMP treatment (Jabs et al., 1997). In addition, elevation acts negatively on PTI (Nicaise et al., 2009; Pandey and of cytoplasmic Ca2þ, which is mediated by an increase in Somssich, 2009). During PTI, activation of the MAPK Ca2þ influx, is a critical step in plant innate immunity cascade leads to the activation of WRKY-type transcription (Nicaise et al., 2009). Plant recognition of PAMPs induces factors and key regulators of plant immunity (Pandey and rapid and transient production of reactive oxygen species Somssich, 2009). Elongation factor Tu (EF-Tu) is one of the (ROS) in an oxidative burst (Zhang et al., 2007), and the most abundant bacterial proteins and is recognized as a PAMP production of RbohD-dependent ROS appears to be down- in Arabidopsis and other Brassicaceae (Kunze et al., 2004; stream or independent of MAPK activation (Nicaise et al., Zipfel et al., 2006). The EF-Tu-derived peptide elf18, a highly 2009). The accumulation of callose, which is synthesized conserved N-acetylated 18-amino acid peptide, is sufficient to between the cell wall and the plasma membrane, as well as trigger immune response. The plant PRR for EF-Tu is the stomatal closure, are classic markers of PTI (Spoel and Dong, LRR-RLK EF-Tu receptor (EFR), which belongs to the same 2008; Bari and Jones, 2009) (Fig. 1). In addition, the SA, JA, subfamily (LRRXII) as FLS2 (Zipfel, 2009). FLS2 and EFR and ethylene defense hormones are induced in PTI (Jones and may oligomerize with BAK1, a general regulator of LRR- Dangl, 2006). RLKs, and other SERK proteins in a ligand-dependent manner (Zipfel, 2009). The two receptor-like proteins ETI LeEIX1 and LeEIX2, which contain a Leucine zipper, an extracellular Leu-rich repeat domain with glycosylation During the development of ETI, plants evolved R genes to signals, a transmembrane domain, and a C-terminal domain detect pathogen effectors and trigger defense responses with a mammalian docytosis signal, have been identified in (Fig. 1), and pathogens, in turn, have evolved new effectors to tomato for perception of the ethylene-inducing xylanase, (Ron evade ETI. Such interactions between R proteins and effectors and Avni, 2004). Chitin is a major constituent of the cell wall oscillate between compatible and incompatible reactions over of most fungi, and products degraded from chitin, N-acetyl- time (Qutob et al., 2006b). Genes encoding pathogen effectors glucosamine and N-acetylchito-oligosaccharides, are potent that induce R gene-mediated resistance are defined as Avr PAMPs in several plant species (Kaku et al., 2006). The rice genes, which qualitatively reduce virulence but only when the chitin-binding protein CEBiP is a transmembrane protein, and host has the cognate R gene (Martin et al., 1993; Oh and silencing of CEBiP in rice reduces chitin binding, suggesting Martin, 2011). Several plant bacterial pathogens contain that it constitutes the chitin PRR (Zipfel, 2009). In legumes, members of the type III secretion system (TTSS) protein a soluble b glucan-binding protein can potentially release and family, which has the ability to deliver bacterial virulence then bind two ligands, 1,6-b-linked and 1,3-b-branched effectors directly into the host cells (He et al., 2004). Pto was  Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 29 the first disease resistance gene cloned from plants, which reprogramming, programmed cell death, and hormonal encodes an intracellular Ser/Thr protein kinase that activates changes are triggered during both PTI and ETI as common ETI in tomato (Oh and Martin, 2011). In concert with Prf, plant immune responses. However, there are differences in a NBS-LRR protein, Pto triggers a resistance response by how plants use these common signaling networks in PTI and interacting with either the AvrPto or AvrPtoB effector proteins ETI. delivered into the plant cell by Pseudomonas syringae pv. Analysis of the Arabidopsis transcriptome using a whole- tomato (Oh and Martin, 2011). During the past 15 years, about genome DNA microarray revealed that exposure to a specific 25 genes that play a role in Pto-mediated ETI have been MAMP treatment induced a large transcriptional response identified by loss-of-function studies (Oh and Martin, 2011). (Navarro et al., 2004; Gust et al., 2007). In addition, the As mentioned above, plants can overcome pathogen transcriptome responses triggered by various MAMPs are very suppression of PTI and re-establish ETI, but it is uncertain similar in the early stages (Navarro et al., 2004), indicating how they do this. During infection of Arabidopsis by Pseu- that these PTI responses involve a common downstream domonas syringae pv tomato DC3000, the pathogen effector signaling mechanism. Interestingly, the genes induced by flg22 HopM1 destabilizes a host ADP ribosylation factor guanine and by effector recognition overlap significantly (Tsuda and nucleotide exchange factor, AtMIN7, through the host 26S Katagiri, 2010), suggesting that ETI may have adapted proteasome (Nomura et al., 2006; Nomura et al., 2011). a part of its immune machinery from the pre-existing PTI, in AtMIN7 is required not only for PTI but also for ETI, and the addition to developing a new set of recognition molecules. HR posttranscriptional AtMIN7 level increases in response to is a form of rapid plant programmed cell death that may activation of PTI (Nomura et al., 2011). Blocking pathogen restrict pathogen growth, which is often associated with ETI. degradation of AtMIN7 is a critical part of the ETI mechanism HR triggered by AvrRps4, which is derived from the bacterial to counter bacterial suppression of PTI. AvrPphB is a cysteine pathogen P. syringae, is dependent on autophagy components, protease that cleaves the Arabidopsis receptor-like cyto- whereas AvrRpt2-triggered HR is not (Hofius et al., 2009), plasmic kinase PBS1 to trigger cytoplasmic immune receptor indicating that mechanisms leading to HR are different among RPS5-specified ETI. It was shown that AvrPphB can inhibit different ETI triggers. Surprisingly, flagellin derived from P. PTI by cleaving PBS1-like (PBL) kinases in plants lacking syringae pv. tabaci6605 induces cell death. Hence, plant cell RPS5. AvrPphB-mediated degradation of PBS1 is monitored death can be mediated by different signaling mechanisms and by RPS5, to initiate ETI, and AvrPphB targets other PBL occur both in PTI and ETI (Tsuda and Katagiri, 2010). ROS kinases for PTI inhibition (Zhang et al., 2010a). SUMM2 is may function as signaling molecules following pathogen a nucleotide-binding leucine-rich repeat (NB-LRR) R protein, recognition, and their generation is one of the earliest cellular and SUMM2-mediated immunity is negatively regulated by responses (Torres et al., 2006; Tsuda and Katagiri, 2010). the MEKK1-MKK1/MKK2-MPK4 cascade. Inhibition of MAMP recognition triggers rapid ROS production, which is MPK4 kinase activity by the Pseudomonas syringae patho- dependent on the NADPH oxidase AtRbohD (Torres et al., genic effector HopAI1 resulted in the activation of SUMM2- 2006), and recognition of a pathogen effector by an R mediated defense responses (Zhang et al., 2012) protein also elicits ROS accumulation (Tsuda and Katagiri, As an indicator of the evolutionary battle between plants 2010). Flg22 perception triggers the activation of the MAPK and pathogens, ETI itself can be suppressed by other effectors. cascade, and MPK3 and MPK6 are also activated by HopZ1a is a P. syringae pv. syringae type III effector, P. syringae infection, and this latter activation is much more a member of the HopZ effector family of Cys-proteases that prolonged than MAMP treatment when P. syringae carries the triggers immunity in Arabidopsis. HopZ1a-triggered immunity effector AvrRpt2 (Tsuda and Katagiri, 2010). Hence, different is independent of salicylic acid (SA), EDS1, jasmonic acid durations of MAPK activity may be the marker to the differ- (JA), and ethylene-dependent pathways. Moreover, HopZ1a entiation of downstream responses between PTI and ETI suppresses the induction of PR-1 and PR-5 associated with (Katagiri, 2004; Liu and Zhang, 2004). In addition, SA, JA, Pto-triggered ETI-like defenses, AvrRpt2-triggered immunity, and ethylene signaling can all be activated in PTI and ETI, but and Pto activation of SAR, and that suppression requires they lead to different outcomes (Tsuda et al., 2008; Grant and HopZ1a Cys protease activity (Macho et al., 2010). Jones, 2009; Halim et al., 2009; Pieterse et al., 2009; Robert- As a PRR, FLS2 not only recognizes a part of bacterial Seilaniantz et al., 2011). In other plants, hormones such as flagellin but also is physically associated with three R proteins, abscisic acid, gibberellins, and auxin also play roles in plant RPM1, RPS2, and RPS5 (Qi et al., 2011), indicating a possible immunity (Robert-Seilaniantz et al., 2011). association of PTI and ETI receptors in Arabidopsis. More- over, PTI and ETI differentially contribute to basal resistance CONTRASTING MODELS OF PATHOGEN (Tsuda and Katagiri, 2010; Zhang et al., 2010b). RECOGNITION BY PLANTS Comparing signaling pathways engaged in PTI and ETI In the 1930s, Flor defined the basic elements of gene-for- gene complementarity in plantepathogen interactions, in PTI and ETI are two separate tiers of the plant immune which single plant resistance genes and single complementary system, but, at least in some cases, PTI and ETI extensively avirulence genes account for plant recognition of pathogens, share downstream signaling machinery. Transcriptional which results in HR (reviewed by Flor, 1971). Functional 30 Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 alleles are generally inherited as dominant characters. If The guard model either partner lacks a functional allele, recognition and resistance do not occur and the plant becomes infected (Keen, There is increasing evidence for indirect interactions 1990). between pathogen effectors and R proteins, resulting in the proposal of the ‘guard hypothesis’ model (Fig. 3A). In this The elicitoresuppressor and elicitorereceptor models model, R proteins guard a limited number of host proteins that are targets of pathogen effectors during pathogenesis (van der There are two main models proposed to explain the Hoorn and Kamoun, 2008). The guard model suggests that molecular basis of recognition and specificity in gene-for-gene multiple effectors can be perceived by a single R protein and systems. In the elicitoresuppressor model, pathogens are that a relatively few R genes can target the broad spectrum of thought to provide general elicitors that initiate defense reac- pathogens that attack plants. This model highlights that the tions in plants until a specific suppressor is produced by guarded effector target (also called the guardee) is indispens- a particular pathogen race (Fig. 2A) (Bushnell and Rowell, able for the virulence function of the effector protein in the 1981; Keen, 1990). The model assumes that many pathogen absence of the cognate R protein (Jones and Dangl, 2006). The species have substances that elicit defense responses in plants, guard model is supported by the findings of RIN4 and PBS1 in and the responses elicited are mostly the production of Arabidopsis and RCR3 and Pto in tomato (Jones and Dangl, phytoalexins and the induction of hypersensitive cell death. 2006). In Arabidopsis, AvrRpm1 and AvrRpt2, two distinct Such defenses are assumed to be elicited nonspecifically by effectors from Pseudomonas species, target the host protein binding of the elicitor to a receptor in the non-host plant. The RIN4, the status of which is closely monitored by the R model further assumes that pathogens produce specific proteins RPM and RPS2 (van der Hoorn and Kamoun, 2008). suppressors, which prevent the nonspecific elicitors from EDS1 (ENHANCED DISEASE SUSCEPTIBILITY1) acting, and the plant becomes infected (Gabriel and Rolfe, behaves as an effector target and activated TIR-NB-LRR 1990). In the elicitorereceptor model, either proteins from signal transducer for defenses across cell compartments primary avirulence genes or metabolites resulting from (Heidrich et al., 2011). elicitor-mediated catalytic activities are predicted to be recognized by specific plant receptors encoded by disease The decoy model resistance genes, and these then trigger the resistance response (Fig. 2B) (Dangl and McDowell, 2006). Both models indicate Recently, many pathogen effectors were found to have the specific recognition of pathogen Avr proteins by plant R multiple targets in the host and the guardee proteins are often proteins, in which the former are the ligands for the latter dispensable for the virulence of effectors in the plants lacking (Mcdowell and Simon, 2006). Although these models provide the R protein (Zipfel and Rathjen, 2008). New data on addi- a simple parallel to the immune system, they are not strongly tional targets of AvrPto and AvrBs3 promoted the concept that supported by molecular evidence for direct interactions some host targets of effectors act as decoys to detect pathogen between R proteins and their cognate Avr proteins. To date, effectors via R proteins (van der Hoorn and Kamoun, 2008). only three pairs of direct R-Avr interactions have been van der Hoorn and Kamoun (2008) proposed the decoy model demonstrated (Jia et al., 2000; Deslandes et al., 2003; Dodds (Fig. 3B) to explain the recent knowledge of evolution in et al., 2006). plantepathogen interactions. This model is based on an Fig. 2. Comparison of the elicitoresuppressor model and the elicitorereceptor model. A: the elicitoresuppressor model. Elicitor initiates plant defense reaction (resistance) until appearance of a specific suppressor in a particular pathogen race, which leads to failure of defense reaction (susceptibility). B: the elicitorereceptor model. Protein encoded by avirulence gene is recognized by a specific plant receptors, which then triggers the resistance response. If the receptor does not fit the avirulence protein, this would inevitably lead to susceptibility.  Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 31 Fig. 3. Comparison of the guard model and the decoy model. A: the guard model. Multiple effectors could be perceived by a single R protein, and a relatively small number of R genes could target the broad spectrum of pathogens that attack plants. B: the decoy model. The guardee is in an evolutionarily unstable situation named as ‘decoy’. In the presence of functional R genes, natural selection is expected to favor guardees with improved interaction with an effector to enhance pathogen detection. In the absence of R genes, natural selection is expected to drive the guardee to decrease its binding affinity with the effector and evade detection and modification by the effector. evolutionary point of view, whereby the guardee is in an APPLICATION OF MAJOR R GENES AND QRLS evolutionarily unstable situation, as it is subjected to two opposing natural selection forces in plant populations where Utilization of major R genes polymorphic R genes are either present or absent. In the presence of functional R genes, natural selection is expected to Although R genes have been extensively used in crop favor guardees with improved interaction with an effector to improvement, there is a high risk because of their potentially enhance pathogen perception. In the absence of R genes, transient effectiveness and availability, as the cognate path- natural selection is expected to drive the guardee to decrease ogen has a high potential for evolving new race specificity. its binding affinity with the effector, and evading detection and One typical example is the outbreak of powdery mildew in modification by the effector then results in a host ‘decoy’ wheat caused by Blumeria graminis (DC.) E.O. Speerf. sp. protein to be relaxed selective constraint during evolution. tritici (Bgt), which overcame several major resistance genes This decoy specializes in effector perception by the R protein. used in the Chinese wheat breeding program (Tao et al., 2000). The P. syringae effector AvrPto binds FLS2 to block plant Although more durable resistance may also be obtained by immune responses in the plant cell and the ability to target wide deployment of multiple R genes, approaches that yield FLS2 is required for the virulence function of AvrPto in plants. long-term effectiveness and long-lasting specificity are needed Pto competes with FLS2 for AvrPto binding, which in asso- in plant resistance breeding (St Clair, 2010). ciation with Prf, recognizes the bacterium and triggers strong resistance (Xiang et al., 2008). The decoy model is distinct Utilization of QRLs from the guard model, which indicates that the manipulation of the guarded effector target benefits pathogen fitness in the Several QRLs have been discovered in numerous crop absence of the R protein. plants, but only a few have been used in breeding programs Although different models have been proposed, each one (Pumphrey et al., 2007). However, the practical use of QRLs might apply to specific pathosystems to explain the complicated indicates that quantitative disease resistance is an exciting field interactions between plants and pathogens. More experimental with the prospect of valuable applications in crop improve- evidence is, however, needed to differentiate between these ment as compared with qualitative resistance, because of its models, which may lead to novel approaches to manipulate plant broad-spectrum and long-lasting resistance. Resistance genes innate immunity and improve pathogen resistance. with minor-to-intermediate additive effects can result in long- 32 Y. Zhang et al. / Journal of Genetics and Genomics 40 (2013) 23e35 lasting resistance to yellow (stripe) and leaf (brown) rusts isolation will be beneficial for the research on molecular caused by Puccinia striiformis and Puccinia triticina, plantemicrobe interactions. respectively (Singh, 2005). Fhb1 is a major QRL for resistance Over the past several years, detailed models for to Fusarium head blight (FHB) in wheat. A total of 19 QTL- plantepathogen interactions have emerged involving recog- NIL pairs were developed by using microsatellite markers nition, evasion, and defense. It does, however, appear likely flanking the QTL region, and each NIL pair was tested under that the molecular basis of plant resistance will draw upon an point-inoculation in a greenhouse (Pumphrey et al., 2007). On even broader mechanistic base. Aspects such as components of average, NILs with Fhb1 significantly (P < 0.001) reduced the the signal transduction system, antimicrobial compounds such disease severity rating by 23% and the percentage of infected as phytoalexins, and other unknown factors are also likely to kernels by 27% in harvested grain. Six QRLs (Rphq1, Rphq2, be important components of plant resistance responses that Rphq3, Rphq4, Rphq5, and Rphq6) resistance to leaf rust remain to be characterized. Cloning additional resistance (causal agent Puccinia hordei) in barley were detected by 103 genes and QTLs that underlie plant resistance will reveal how recombinant inbred lines (RILs) by single-seed descent from they contribute to plant defenses. This knowledge will enable a cross between the susceptible parent L94 and the partially more efficient and effective utilization of these genes in crop resistant parent Vada (Qi et al., 1998), and three of them improvement and protection. (Rphq2, Rphq3, and Rphq4) were confirmed by using NILs created by marker-assisted backcrossing (MAB) (van Berloo ACKNOWLEDGEMENTS et al., 2001). The QRL Rphq2 was introgressed by MAB into the susceptible L94 background to obtain NIL L94- This study was financially supported by the National Basic Rphq2. By contrast, NIL Vada-rphq2 contained a susceptibility Research Development Program of China (Grant No. allele in the resistant Vada background. The latency period 2009CB118401), and the National High-tech Research and was prolonged by 28 h for L94-Rphq2 and shortened by 23 h Development Program of China (Grant Nos. 2012AA10A305 for Vada-rphq2 (Marcel et al., 2007), and this delay is suffi- and 2012AA101104). cient to help keep the damage below economic thresholds for pesticide treatment. In bean, common bacterial blight is caused by Xanthomonas axonopodis pv. phaseoli. Mutlu and REFERENCES colleagues developed the advanced backcross bean lines NE- 01-8, NE-01-15, and NE-01-17, which possess the QTL on Aarts, N., Metz, M., Holub, E., Staskawicz, B.J., Daniels, M.J., Parker, J.E., linkage group B8 derived from the highly resistant line XAN 1998. 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