Deciphering the Molecular Interplay Between Wheat and Puccinia striiformis f. sp. Tritici: Mechanisms of Interaction and Resistance Strategies

ABSTRACT

Wheat stripe rust, caused by the obligate biotroph Puccinia striiformis f. sp. tritici (Pst), remains one of the most destructive fungal diseases threatening global wheat production. Beyond traditional control through chemical application and resistant cultivar breeding, rapid advances in molecular biology have substantially reshaped our understanding of the intricate molecular dialogue between wheat and Pst. In recent years, research has increasingly focused on Pst pathogenicity factors, wheat immune perception, and the multilayered signaling networks that orchestrate defense responses. Particularly, studies of the molecular crosstalk spanning PAMP recognition, effector deployment, immune activation, and host‐pathogen metabolic exchanges have revealed highly dynamic and sophisticated interaction strategies employed by both organisms. A systematic overview of these molecular processes is essential for advancing host resistance breeding and for guiding the rational design of novel disease‐management strategies. Here, we comprehensively synthesize current knowledge of the molecular mechanisms underlying wheat–Pst interactions, highlight key advances in understanding their reciprocal communication, and discuss emerging directions for developing durable resistance.

1. Introduction

Rust fungi constitute a diverse group of obligate biotrophic pathogens, with over 7000 species reported worldwide (Duplessis et al. 2021). These fungi typically produce yellow or rust‐colored lesions and are responsible for numerous economically significant diseases in agricultural and forest ecosystems (Zhao and Kang 2023). Among them, wheat rust diseases—including stem rust (Sr), leaf rust (Lr), and stripe (yellow) rust (Yr)—are caused by Puccinia graminis f. sp. tritici (Pgt), Puccinia triticina (Pt), and Puccinia striiformis f. sp. tritici (Pst), respectively. In contrast to Pgt and Pt, Pst is well adapted to cooler environments, posing a particular threat to wheat grown in high‐latitude regions (Zhao and Kang 2023). Under cool and humid conditions, Pst produces airborne urediniospores that germinate on the leaf surface, forming germ tubes that locate and penetrate stomata (Kang et al. 2002). Following stomatal entry, substomatal vesicles, haustorial mother cells (HMCs), infection hyphae, and branched hyphal networks are formed sequentially (Kang et al. 1994; Chen et al. 2014). Subsequently, HMCs differentiate into haustoria, specialized feeding structures that serve as key interfaces for nutrient uptake and molecular exchange between the pathogen and host (Chen et al. 2014; Xu et al. 2020).

Plant immunity against pathogens relies on a multilayered defense system. The first layer involves the recognition of conserved pathogen‐associated molecular patterns (PAMPs), such as peptides, proteins, lipids, and polysaccharides, by pattern recognition receptors (PRRs) located on the plant cell surface (Schwessinger 2017; Ngou et al. 2024). This recognition activates pattern‐triggered immunity (PTI), characterized by defense responses including callose deposition and the rapid production of reactive oxygen species (ROS) (Boller and He 2009; Sanabria et al. 2010). To counteract PTI, biotrophic pathogens such as Pst secrete effector proteins from haustoria to suppress host immunity and facilitate colonization (Yoshida et al. 2016; Mapuranga et al. 2022). In turn, plants have evolved intracellular immune receptors, primarily nucleotide‐binding leucine‐rich repeat (NLR) proteins, to detect these effectors and activate a second layer of defense known as effector‐triggered immunity (ETI) (Wang, Hu, Wang, et al. 2019; Wang et al. 2023). Immune signals are further transduced intracellularly, resulting in the accumulation of defense proteins and antimicrobial compounds that either directly inhibit pathogen growth or induce localized cell death to limit nutrient availability. This review consolidates years of research on the molecular mechanisms underlying the wheat–Pst interaction, proposing new research directions to further our understanding of this interaction and to develop strategies for controlling wheat stripe rust.

2. Material Transfer from Pst to Wheat

Upon contact, Pst hyphae penetrate the wheat cell wall and establish a close host association, triggering PTI via PAMP recognition (Wang et al. 2024). In response, Pst deploys enzymes, effectors, and noncoding RNAs to suppress host immunity, some of which may also be perceived as invasion signals by the host (Tariqjaveed et al. 2021).

2.1. Functional Proteins Secreted by Pst Into the Apoplast

The plant cell wall, composed of polysaccharides and glycoproteins, serves as the primary physical barrier against pathogen invasion (Kovács 2024; Molina et al. 2024). Many pathogens (e.g., Phytophthora sojae, Magnaporthe oryzae) secrete GH12 family hydrolases to degrade host cell walls and facilitate infection (Ma et al. 2015; Xia et al. 2020). The products of these cell wall‐degrading enzymes or the enzymes themselves act as critical signals enabling plants to detect pathogen invasion (Takeda et al. 2010). However, for Pst, only the secretory pectinase gene PsPL1 has been confirmed to be upregulated during infection (Li et al. 2016). Therefore, the secretion dynamics and functional mechanisms of cell wall‐degrading enzymes during early wheat–Pst interactions urgently require further elucidation.

Once Pst penetrates the wheat cell wall, host PTI receptors recognize PAMPs and initiate defense responses. Studies have shown that Pst infection is accompanied by increased abundance of chitinase and β‐1,3‐glucanase (Kang et al. 2003; Han et al. 2006). Chitin oligomers within the stripe rust fungus cell wall can induce plant PTI responses (Xiao et al. 2023). To evade wheat PTI, Pst secretes chitin deacetylase PsCDA2, which modifies its own cell wall chitin, reducing its recognition by host chitinases (Xiao et al. 2023). In response to pathogen attack, plants generate reactive oxygen species (ROS) as a defense mechanism. To counteract this, Pst secretes catalase PsCAT1 (Yuan, Qian, et al. 2021) and superoxide dismutase PsSOD1 (Liu, Guan, et al. 2016) to neutralize the oxidative burst, thereby mitigating host defenses.

Most of Pst's metabolic and energy demands during infection and colonization are derived from the host. The invertase PsINV is secreted by Pst into the extrahaustorial matrix at the wheat–Pst interface and enzymatically catalyzes the conversion of wheat‐secreted sucrose into glucose and fructose (Chang et al. 2017), which are then transported into the haustorium via hexose transporters (HXT) to sustain Pst metabolism (Chang et al. 2020). Notably, the hexose transporter PsHXT1 has been characterized as a glucose‐proton symporter critical for optimizing sugar utilization efficiency and is indispensable for Pst pathogenicity (Chang et al. 2020). Together, these findings reveal that Pst's apoplastic colonization relies on a coordinated strategy: suppressing host immunity via ROS scavenging and chitin modification, while hijacking host sucrose to fuel its energy metabolism.

2.2. Effectors Secreted by Pst Into Wheat Cells

To suppress the host innate immune response, Pst secretes a diverse repertoire of effectors into wheat cells (Ngou et al. 2022; Wang, Pruitt, et al. 2022). This suppressive mechanism operates at multiple complex levels, characterized predominantly by two modes: some effectors obstruct the function of genes associated with defense signaling pathways, while others promote the expression or activity of disease‐susceptibility genes (Table 1).

TABLE 1.

Published Pst effectors and their associated types of immune suppression.

Effector	Function	Target	References
PstGSRE1	Inhibition of disease‐related transcription factor activity	TaLOL2	Qi et al. (2019)
Pst21674		TaASR3	Zheng et al. (2023)
Pst3180.3		TaMYB4L	Shu et al. (2024)
Hasp170		TaPSTE	Yan et al. (2026)
Pst_A23	Inhibition of functional transcript production of disease resistance genes	TaXa21‐H	Tang et al. (2022)
		TaWRKY53
Hasp98	Inhibition of disease‐related kinase activity	TaMAPK4	Wei et al. (2023)
PEC6		TaADK	Liu, Pedersen, et al. (2016)
Pst03724		TaCaM3‐2B	Wang et al. (2024)
HASP215		TaMKK2	Shu et al. (2025)
PstCFEM2		TaCIPK9	Zhang, Guo, et al. (2026)
Pst12806	Inhibition of wheat leaf photosynthesis	TaISP	Xu et al. (2019)
Pst_4			Wang, Zhai, et al. (2021)
Pst_5
PstCEP1		TaFd1	Bao et al. (2023)
Pst_TTP1		TaTrx	Li et al. (2025)
PstCRT	Inhibition ER stress‐mediated HR	TaHRLI	Guo et al. (2026)
PstGTA1 Pst15882	Facilitation of pathogen susceptibility gene expression	TaSIG TaMYB50	Duan et al. (2024) and Zheng et al. (2025)
Pst18363	Stabilization of pathogen susceptibility enzyme activity	TaNUDX23	Yang et al. (2020)
PsSpg1		TaPsIPK1	Wang, Tang, et al. (2022)
Pst27791		TaRaf46	Wan et al. (2022)
PstGSRE4		TaGAPDH2	Liu, Wang, et al. (2024)
Pst11215		TaVDAC1	Pan et al. (2024)
PsSRPKL	Uncharacterized function but suppresses disease resistance		Cheng et al. (2015)
Ps87			Gu et al. (2011)
PSTha5a23			Cheng et al. (2017)
PSEC2			Su et al. (2021)
PSEC17
PSEC45
PstCFEM1			Bai et al. (2022)
Pst_8713			Zhao et al. (2018)

2.2.1. Suppression of Resistance Gene Function

To suppress wheat resistance, Pst deploys a suite of effectors that target multiple nodes in the host defense network, including transcription factors, protein kinases, and chloroplast‐localized proteins. Regarding transcriptional regulation, PstGSRE1 disrupts TaLOL2 nuclear localization (Qi et al. 2019), Pst21674 binds TaASR3 to prevent its polymerization (Zheng et al. 2023), and Pst_A23 interferes with TaXa21‐H and TaWRKY53 transcription (Tang et al. 2022). Hasp170 directly disrupts the phase separation of the host nuclear protein TaPSTE, blocking TaNF‐YC recruitment and suppressing ROS and Ca²⁺‐mediated immunity (Yan et al. 2026a), while Pst3180.3 inhibits TaMYB4L transcriptional activity to reduce resistance (Shu et al. 2024). Targeting kinase signaling, PEC6 affects TaADK (Liu, Pedersen, et al. 2016), Hasp98 inhibits TaMAPK4 (Wei et al. 2023), HASP215 disrupts the TaMKK2‐TaMAPK6‐TaSGT1 cascade (Shu et al. 2025), and Pst03724 competes with TaCaM3‐2B for TaNADK2 binding, weakening resistance gene activation (Wang et al. 2024). To disrupt photosynthesis, Pst_12806, Pst_4, and Pst_5 target TaISP (Xu et al. 2019; Wang, Zhai, et al. 2021), PstCEP1 targets TaFd1 (Bao et al. 2023), and Pst_TTP1 blocks TaTrx import, delaying senescence and suppressing H₂O₂ defenses (Li et al. 2025). Additionally, PstCRT mimics host TaCRT to competitively bind TaHRLI, blocking endoplasmic reticulum (ER) translocation and suppressing ER stress‐mediated HR; an engineered TaHRLI^Mut evades this effector and confers broad‐spectrum resistance (Guo et al. 2026) (Figure 1). Collectively, these findings illustrate that Pst effectors have evolved convergent strategies to suppress host immunity by interfering with transcriptional regulation, kinase signaling, and photosynthetic metabolism (Figure 1). Understanding how wheat counteracts these mechanisms—through decoy receptors or effector‐insensitive host variants—offers a promising direction for engineering durable resistance.

FIGURE 1.

The molecular response model of wheat upon perception of Pst. The PAMPs of Pst are recognized by PRRs on the wheat cell surface, triggering intracellular signaling cascades such as MAPK pathways, calcium‐dependent signaling, and ROS generation, ultimately transmitting defense signals to the nucleus. Effectors secreted by Pst target host immune responses, aiming to suppress PTI and ETI. However, certain NLR receptors detect these effectors and initiate defense mechanisms. Based on the Sr35 disease resistance model in wheat, it is hypothesized that NLR proteins may oligomerize into resistosomes upon Pst effector recognition, mediating calcium (Ca²⁺) influx as part of the HR. Intracellular Ca²⁺ oscillations modulate the activity of Calcineurin B‐like interacting protein kinases (CIPKs) and calcium‐dependent protein kinases (CDPKs). These kinases phosphorylate key transcription factors, such as WRKYs, MYBs, and NACs, enhancing the expression of defense‐related genes. Emerging evidence suggests that NLR proteins may directly translocate to the nucleus upon Pst effector recognition, facilitating transcriptional reprogramming of defense responses. Upon nuclear transduction of resistance signals, the upregulation of defense‐related genes, such as TaPR1, TaAbc1, and TaMCA1, enhances ROS accumulation. This process triggers a HR and programmed cell death (PCD), restricting Pst proliferation and nutrient acquisition. Moreover, Pst effectors modulate host susceptibility (S) genes, such as TaPsIPK1 and TaSWEET14d, stabilizing or activating TFs and kinases that promote pathogen fitness. This enhances Pst nutrient acquisition and systemic colonization. This effector‐mediated modulation often enhances the function of S genes, thereby assisting Pst in nutrient acquisition and facilitating its further growth.

2.2.2. Promotion of Susceptibility Gene Function

Susceptibility (S) genes are host genes that can be exploited by pathogens to aid colonization and subsequent proliferation, essential for successful invasion and establishment (Taj et al. 2022; Baruah et al. 2025). Accordingly, some Pst effectors promote the expression of S genes or stabilize S proteins, processes essential for pathogen colonization (Table 1). For instance, PsSpg1 hijacks the wheat kinase TaPsIPK1, enhancing its phosphorylation and nuclear translocation; in the nucleus, TaPsIPK1 phosphorylates the TF TaCBF1, suppressing resistance genes while boosting TaPsIPK1 expression, thereby increasing susceptibility (Wang, Tang, et al. 2022). Similarly, PstGTA1 targets the promoter of the negative immune regulator TaSIG, possibly activating it via histone H3K4 acetylation (Duan et al. 2024). Beyond TFs, several effectors stabilize susceptibility‐related enzymes: Pst18363 stabilizes TaNUDX23 to reduce ROS accumulation, Pst27791 stabilizes the Raf‐like kinase TaRaf46, and PstGSRE4 stabilizes TaGAPDH2, all suppressing host immunity (Yang et al. 2020; Wan et al. 2022; Liu, Wang, et al. 2024) (Figure 1). Other effectors manipulate ROS scavenging and subcellular localization: Pst9653 blocks TaCAT3 translocation to peroxisomes, accelerating ROS clearance (Wei et al. 2025), while Pst11215 promotes TaVDAC1 ubiquitination, driving ROS export from mitochondria to protect against immune‐mediated necrosis (Pan et al. 2024) (Figure 1). Finally, some effectors reprogram host metabolism and ion flux: Pst15882 derepresses the sucrose transporter TaSWEET14d to allocate sugars to the fungus (Zheng et al. 2025), and PstCFEM2 competitively binds TaHA2 with TaCIPK9, causing apoplastic acidification and stomatal opening to favor infection (Zhang, Guo, et al. 2026). Collectively, these examples illustrate that Pst effectors converge on promoting host susceptibility through diverse molecular mechanisms, from transcriptional reprogramming to protein stabilization and metabolic modulation (Figure 1). The convergence on promoting susceptibility gene function highlights a critical vulnerability: if key S genes or their regulatory pathways can be disrupted or edited, broad‐spectrum and durable resistance may be achieved. Future efforts should prioritize identifying core S gene networks targeted by multiple effectors and developing CRISPR‐based strategies to knockout or modify these genes without compromising plant fitness.

2.3. Noncoding RNAs in Pst Infection

Noncoding RNAs (ncRNAs), including small RNAs (sRNAs), regulate gene expression via RNA interference (RNAi) (Weiberg et al. 2014; Qiao et al. 2021). By exploiting sequence complementarity, sRNAs regulate target gene expression through transcriptional repression, transcript cleavage, or translation inhibition (Ghildiyal and Zamore 2009). Furthermore, the mobility of sRNAs enables them to manipulate target gene expression across organisms engaged in intimate symbiotic relationships (Liu and Chen 2018; Hudzik et al. 2020). In the context of wheat infection by Pst, many microRNAs (miRNAs) are secreted into wheat cells by the pathogen to dampen the expression of resistance genes (Mueth et al. 2015; Mueth and Hulbert 2022). These targeted genes include those encoding NBS‐LRR proteins, receptor‐like proteins and kinases (RLP/RLKs), ABC transporters, MYB TFs, serine/threonine protein kinases, WD repeat‐containing proteins, and endoribonuclease dicer (Mueth et al. 2015) (Figure 1). Currently, Pst‐milR1 is the first known microRNA‐like RNA (milRNA) from Pst; it targets wheat TaPR2 to facilitate infection (Wang, Sun, et al. 2017) (Figure 1). Silencing of the Pst‐milR1 precursor leads to enhanced wheat resistance against the virulent Pst race CYR31 (Wang, Sun, et al. 2017). The discovery of Pst‐milR1 provides a novel framework for investigating the roles of noncoding RNAs in Pst–wheat interactions. Together, these observations reveal that Pst exploits ncRNAs as molecular tools to silence wheat defense genes. Harnessing this knowledge—for instance, by blocking fungal sRNAs or editing their host targets—offers new opportunities for developing RNAi‐based resistance against stripe rust.

3. Wheat Recognition of Pst

When Pst hyphae contact wheat mesophyll cells, fungal surface molecules (PAMPs) are recognized by host cell‐surface receptors, activating PTI (Liu et al. 2023). However, Pst rapidly secretes effectors to suppress PTI. In turn, wheat has evolved intracellular NLR receptors that recognize these effectors and trigger ETI (Xiao et al. 2025) (Figure 2).

FIGURE 2.

The molecular mechanism model of WKS1.1 (Yr36) resistance to wheat stripe rust disease. The Yr36 disease‐resistant transcript encodes the protein WKS1.1, which is localized in the chloroplast. WKS1.1 phosphorylates tAPX and ZEP1, leading to the inhibition of their enzymatic activity in H₂O₂ degradation, thereby facilitating ROS accumulation. Furthermore, WKS1.1 phosphorylates PsbO, a component of PSII, leading to impaired electron transport and reduced photosynthetic efficiency. WKS1.1 phosphorylates KAT‐2B, enhancing its ability to synthesize JA (Jasmonic Acid), which subsequently upregulates ROS‐related gene expression. WKS1.1 phosphorylates SPS1‐B, suppressing its enzymatic activity and thereby curbing sucrose transport to Pst. By phosphorylating these target proteins, WKS1.1 modulates their activity, resulting in elevated ROS levels, leaf chlorosis, and programmed cell death, ultimately restricting Pst proliferation in wheat leaves.

3.1. Recognition by PTI Receptors

PTI is crucial in limiting pathogen invasion, with PTI receptors initiating plant defense responses (Yuan, Ngou, et al. 2021). The first putative rust‐recognition receptor‐like kinase, LRK10, was identified within the Lr10 locus (Feuillet et al. 1997). Subsequently, a receptor‐like protein kinase, RPG1, was discovered in barley and shown to respond to Pgt infection; it undergoes ubiquitination and degradation during infection by avirulent Pgt pathotypes (MCC or SCCL‐C7a), but not by virulent ones (Nirmala et al. 2007). Using gene chip analysis, a wheat receptor‐like protein gene, TaRLP1.1, was identified as being specifically induced by Pst in resistant wheat varieties. Further investigation revealed that TaRLP1.1 plays a substantial role in initiating the hypersensitive response (HR) during pathogen–host interactions, thereby positively regulating resistance to Pst (Jiang et al. 2013). Another wheat cysteine‐rich receptor‐like kinase gene, TaCRK10, was found to be induced following Pst inoculation and high‐temperature treatment; upon recognizing Pst signals, it phosphorylates the histone variant TaH2A.1 to facilitate resistance signal transmission (Wang, Wang, et al. 2021). In Triticum urartu , a leucine‐rich repeat receptor‐like kinase encoded by TuRLK1 was identified and shown to be crucial for YrU1‐mediated resistance against Pst and other pathogens, including powdery mildew (Zou et al. 2022). Additional wheat leucine‐rich repeat receptor‐like kinases, such as TaXa21 (Wang, Wang, Shang, et al. 2019), TaBle IR1 (Sun et al. 2023), and TaSERK1 (Shi et al. 2023), have also been demonstrated to positively regulate stripe rust resistance. Together, these findings indicate that while wheat possesses functional PTI receptors for Pst, the identity of the recognized PAMPs and the downstream signaling network remain elusive. Unraveling these early recognition events will be critical for harnessing PTI in resistance breeding.

3.2. Recognition by ETI Receptors

Plant recognition of pathogen effectors predominantly relies on NLRs, which can identify pathogen molecules either directly or indirectly (Jones et al. 2016). Most NLRs contain three domains: an N‐terminal variable domain, an NBS domain, and a C‐terminal LRR (Wang, Hu, Wang, et al. 2019; Wang et al. 2023). Among the few cloned rust resistance genes in wheat and its relatives, Yr6 (Wu et al. 2025), Yr9 (Wang et al. 2025; Yu et al. 2025), Yr28 (Zhang et al. 2019), Yr84 (Klymiuk et al. 2018), Yr87 (Sharma et al. 2024), and YrTD121 (Hu et al. 2025) encode typical NLR proteins, whereas Yr5, Yr7, and YrSP encode NLRs with an additional zinc‐finger BED domain (Marchal et al. 2018). YrU1 encodes a CC‐NBS‐LRR NLR protein with an N‐terminal ankyrin‐repeat and a C‐terminal WRKY domain (Wang et al. 2020). All these NLR genes mediate leaf cell death at Pst infection sites, indicating that they recognize Pst effectors and trigger ETI responses.

Current studies in other pathosystems have shown that upon recognition of bacterial effectors, certain NLRs can oligomerize to form homopolymers and act as Ca²⁺ channels, mediating an increase in intracellular calcium concentration and thereby activating downstream immune responses (Figure 1). Examples include ZAR1 (Wang, Wang, Hu, et al. 2019; Bi et al. 2021), Sr35 (Förderer et al. 2022; Zhao et al. 2022), NRC4 (Liu, Yang, et al. 2024), and WAI3. Some NLRs can directly interact with downstream proteins to regulate resistance functions, as demonstrated for Sw‐5b (Zhao et al. 2021) and Tsw (Chen et al. 2023). However, the mechanisms by which NLRs recognize Pst effectors, transduce these signals into disease resistance, and propagate signals downstream remain poorly understood. Engineering these NLRs holds promise for creating novel resistance genes or enhancing their broad‐spectrum resistance.

4. Transmission of Defense Signals

After wheat PTI or ETI receptors precisely recognize pathogenic molecules from Pst, these signals are converted into intracellular signals (Chang et al. 2022), including cAMP, cGMP, plant hormones, and Ca²⁺ signals (Khan et al. 2018; Yu et al. 2022; Wang et al. 2023). These cascades involve the activation of protein kinases and TFs, amplifying the expression of downstream defense‐related genes (Chang et al. 2022) (Figure 1). Consequently, wheat activates a series of resistance responses, inhibiting Pst colonization and preventing successful pathogen establishment.

4.1. Protein Kinase‐Mediated Phosphorylation

Protein phosphorylation is a key posttranslational modification that orchestrates signaling cascades essential for plant growth, development, and stress responses (Zhang et al. 2023). Through phosphorylation, kinases modulate signaling pathways, enabling plants to respond to internal and external cues. The Yr36 gene, the first cloned wheat gene conferring stripe rust resistance, encodes WKS1, with the WKS1.1 isoform conferring resistance and WKS1.2 being susceptible (Fu et al. 2009; Gou et al. 2015). WKS1.1 phosphorylates multiple targets—including tAPX, ZEP1, PsbO, TaKAT‐2B, and SPS1‐B—to reduce ROS scavenging, enhance jasmonic acid synthesis, reduce photosynthetic efficiency, and limit sucrose allocation, collectively promoting resistance (Gou et al. 2015; Wang, Li, Wang, et al. 2019; Chang et al. 2023; Yan et al. 2023, 2025) (Figure 2). Thus, wheat uses WKS1.1 to fine‐tune protein activity, enabling a rapid growth‐to‐defense transition under stress. Beyond WKS1.1, other kinases such as TaCIPK5, TaCIPK10, TaCIPK14, and TaCDPK7 also positively regulate resistance (Figure 1). For instance, TaCIPK10 phosphorylates TaNH2 to enhance defense (Liu et al. 2019). Notably, involvement of these Ca²⁺‐related kinases suggests that upstream Ca²⁺ channels respond to Pst infection and trigger Ca²⁺ fluctuations (Figure 1). This supports the idea that wheat NLRs, upon effector recognition, may act as Ca²⁺ channels similar to ZAR1 and Sr35, thereby activating downstream immune responses. MAPKs like TaMAPK4 also contribute, though they can be suppressed by effectors such as Hasp98 (Wang, Song, et al. 2018; Wei et al. 2023) (Table 1). Together, these findings underscore the pivotal role of protein kinases in orchestrating wheat resistance to Pst. Harnessing this knowledge—by engineering effector‐resistant kinase alleles or enhancing Ca²⁺ signaling crosstalk—holds promise for developing durable stripe rust control.

4.2. Activation of TFs

Pathogen invasion often triggers plant transcriptional reprogramming, in which the activation of TFs plays a central role. Upon pathogen invasion, TFs orchestrate transcriptome changes, fine‐tuning gene expression and regulating mRNA abundance, thereby influencing defense‐related gene functions (Amorim et al. 2017; John et al. 2021). Members of the NAC, AP2/ERF, WRKY, and MYB TF families play positive or negative regulatory roles in stripe rust resistance (Table 2). Furthermore, the wheat homolog of AtEIN3, TaEIL1, negatively regulates wheat resistance to Pst (Duan, Wang, et al. 2013). Conversely, the BES/BZR TF TaBle ZR2 promotes the expression of wheat chitinase gene TaCht20.2, enhances total chitinase activity, and confers broad‐spectrum resistance to Pst (Bai et al. 2021) (Table 2). The atypical TF histidine‐rich protein TaHRP1 modulates the expression of photosynthesis‐associated nuclear genes (PhANGs) (Table 2), influencing chloroplast‐produced ROS and optimizing photosynthetic efficiency, thereby enhancing wheat resistance to Pst (Zhang et al. 2024). Pst resistance‐related TFs such as TaAP2‐10, TaAP2‐15, TaWRKY49, TaWRKY10, TaMYB29, TaLHY, and TaMYB391 are also upregulated by SA (Zhang et al. 2015; Wang, Tao, et al. 2017; Hawku et al. 2021, 2022; Zhu, Li, Tang, et al. 2021; Zhu, Li, He, et al. 2021; Hu et al. 2023). The multifaceted roles of these TFs—whether positively modulating resistance or being exploited by pathogen effectors—highlight the intricate balance plants must maintain to effectively defend against pathogens like Pst (Table 1).

TABLE 2.

Transcription factors from wheat that function during wheat—Pst interactions and their classification as reported in published research.

Gene	Family	Resistance to Pst (positive/negative)	References
YrNAM	NACs	Positive	Ni et al. (2023)
TaNAC1		Negative	Wang et al. (2015)
TuNAC69		Positive	Xu et al. (2022)
TaNAC30		Negative	Wang, Wei, et al. (2018)
TaNAC21/22		Negative	Feng et al. (2014)
TaAP2‐15	AP2/ERFs	Positive	Hawku et al. (2021)
TaAP2‐10		Positive	Hu et al. (2023)
wAP2		Positive	Yan et al. (2025)
TaWRKY49	WRKYs	Positive	Wang, Tao, et al. (2017)
TaWRKY62		Positive
TaWRKY76		Positive	Wang, Wang, Shang, et al. (2019)
TaWRKY10		Positive	Zhu, Li, Tang, et al. (2021)
TaWRKY19		Negative	Wang, Fan, et al. (2022)
TaMYB29	MYBs	Positive	Zhu, Li, He, et al. (2021)
TaLHY		Positive	Zhang et al. (2015)
TaMYB391		Positive	Hawku et al. (2022)
TaMYB3		Positive	Feng et al. (2013)
TaMYB4L		Positive	Shu et al. (2024)
TaMYB50		Positive	Zheng et al. (2025)
TaEIL1	EIN3/EILs	Negative	Duan, Wang, et al. (2013)
Table ZR2	BES/BZRs	positive	(Bai et al. 2021)
TaHRP1	histidine‐rich protein	Positive	Zhang et al. (2024)

4.3. Downstream Functional Proteins: Positive and Negative Regulators of Wheat Resistance

Downstream resistance genes generally participate in programmed cell death (PCD), thereby preventing stripe rust colonization and spread. Positive regulators of resistance include PCD‐associated proteins such as TaYSL1A (Islam et al. 2020), TaRar1 (Wang, Wang, et al. 2017), TaARPC3 (Qi et al. 2017), TaATG8j (Mamun et al. 2018), TaMCA1 (Hao et al. 2016) and TaMCA4 (Wang et al. 2012), and TaHIR1/3 (Duan, Guo, et al. 2013); pathogenesis‐related proteins TaPR1, TaPR2, and TaPR5 (Wang, Shen, et al. 2022); and E3 ubiquitin ligases RFEL1 (Qiao et al. 2025) and TaTLP5 (Zhang, Yu, et al. 2026). Notably, the CAPE1 motif in TaPR1 inhibits Pst growth in vitro, and RFEL1 promotes degradation of the SA receptor TaNPR3 (Qiao et al. 2025), while TaTLP5 elevates ROS via TaCAT1 degradation (Zhang, Yu, et al. 2026). Other positive regulators with unknown mechanisms, such as TaCLP1, TaNTF2 (Zhang et al. 2018), and TaHSC70 (Duan, Guo, et al. 2013), are also induced by Pst, underscoring the importance of defense gene upregulation. Conversely, negative regulators (susceptibility genes) include TaMDAR6 (Abou‐Attia et al. 2016), TaClpS1 (Yang et al. 2020), and TaLSD1 (Guo et al. 2013) (inhibiting PCD); TaBln1 (Guo et al. 2022) (disrupting Ca²⁺ influx); TaCSN5 (Bai et al. 2021) (reducing SA accumulation); chloroplast‐localized TaAAED1 (Liu et al. 2021) and TaCSP41a (Liu et al. 2021; Corredor‐Moreno et al. 2022); and the E3 ligase TaPIR1 (Zhang et al. 2024), which degrades TaHRP1 to suppress photosynthesis and ROS production. Given the conserved nature of wheat–Pst affinity, editing susceptibility genes offers a strategy for broad‐spectrum resistance. However, because these genes may also support beneficial microbiota (Chakraborty 2023; Pereira et al. 2023), rigorous validation is required before their modification. Together, these observations highlight the complex network of downstream proteins that both positively and negatively regulate wheat resistance to Pst. Editing susceptibility genes offers a promising path toward durable resistance, but must be balanced against potential effects on plant growth and beneficial microbes. Future work should prioritize functional validation of core S genes and the development of precision editing strategies.

5. Conclusion and Future Prospects

As a persistent threat to global wheat production (Zhan et al. 2022; Li et al. 2023), Pst has co‐evolved with wheat into a highly specialized host‐pathogen relationship. Deciphering this molecular dialogue is key to disrupting compatibility and developing sustainable control. Pst infection relies on four interconnected processes: efficient effector delivery, insufficient host perception, suppression of immunity, and nutrient diversion. Counteracting these—by blocking effectors, enhancing receptor systems, reinforcing immune signaling, and restricting nutrient flow—offers a rational roadmap for durable resistance (Figure 3).

FIGURE 3.

Factors contributing to Pst colonization of wheat and host counter‐defense strategies. The infection and colonization of wheat by Pst are primarily due to the transport of Pst pathogenic molecules to wheat, inadequate recognition of these pathogen molecules by wheat, a weak resistance response in wheat, and the transfer of nutrients to Pst. To counteract these processes, strategies can be focused on: Blocking the delivery of Pst pathogenic molecules, helping wheat to fully recognize Pst's pathogenic molecules, establishing a strong and effective resistance response, and impeding the transfer of nutrients to Pst. These approaches can provide wheat with an advantage in its defense against Pst. Created in BioRender.

Despite the identification of 15 Yr genes (Hu et al. 2025; Wu et al. 2025), only Yr36 has been mechanistically well characterized. This highlights a critical gap: unlike bacterial systems, where NLR resistosome formation and Ca²⁺ channel activity are established, how wheat NLRs recognize Pst effectors remains elusive. Engineering synthetic NLRs or effector‐insensitive host targets (e.g., kinase variants) represents a transformative opportunity. Moreover, the emerging paradigm of pathogen manipulation of host phase separation (Yan et al. 2026) and the successful engineering of host proteins to evade effector recognition open new avenues (Guo et al. 2026). Future efforts should integrate AI‐based effector prediction, CRISPR editing of susceptibility genes, and synthetic biology to create broad‐spectrum resistance. Ultimately, combining resistance gene stacking with precise S gene modification will provide a more effective molecular foundation for durable stripe rust control.

Author Contributions

J. Qu and M. Sajjad drew figures and wrote the manuscript. F. Ye and B. Liu helped collect references and organize the tables. J. Wu provided suggestions and revised the manuscript. All authors approved the final paper.

Funding

This work was supported by National Natural Science Foundation of China (32372102), Shandong Province Key Research and Development Plan (Major Scientific and Technological Innovation Project) (2023TZXD086), and National Major Innovation Platform Supporting Project (2024GZPT01).

Disclosure

No AI tools were used to generate scientific content or interpret data.

Conflicts of Interest

The authors declare no conflicts of interest.

Qu, J. , Ye F., Liu B., Sajjad M., and Wu J.. 2026. “Deciphering the Molecular Interplay Between Wheat and Puccinia striiformis f. sp. Tritici: Mechanisms of Interaction and Resistance Strategies.” Physiologia Plantarum 178, no. 4: e71052. 10.1111/ppl.71052.

Data Availability Statement

Data sharing is not applicable to this article, as no new data were created or analyzed in this study.