Fungal effectors are proteins or non-proteinaceous molecules (such as RNAs or small molecules) secreted by pathogenic fungi into a host organism in order to modulate the host's immune response. [1] [2] [3]
Fungal effectors are proteins or non-proteinaceous molecules (such as RNAs or small molecules) secreted by pathogenic fungi into a host organism in order to modulate the host's immune response. [1] [2] [3]
In the first stages of infection, conserved molecules from the fungal pathogen's cell wall, such as polysaccharides and chitin, are recognised by membrane-localised pattern recognition receptors (PRRs) on the plant host's side. Such conserved molecules are generally described as pathogen-associated molecular patterns (PAMPs) or microbe-associated molecular patterns (MAMPs) and the initial innate immune response that their recognition triggers is known as PAMP-triggered immunity (PTI). [4]
In order to counteract PTI, fungal pathogens secrete effector proteins into the host, some of which may directly inhibit components of the innate immune response cascade. One example is the conserved effector NIS1, present in fungal pathogens from the Ascomycota and Basidiomycota phyla. NIS1 blocks PAMP-triggered immune responses by interacting with the PRR-associated kinases BAK1 and BIK1 and preventing these kinases from interacting with their downstream partners. [5] To protect themselves from the actions of effector proteins, plants have evolved resistance proteins (R proteins), which may in turn recognise an effector and trigger a second tier of immune responses, known as effector-triggered immunity (ETI).
Plant pathogenic fungi use two distinct effector secretion systems and each secretory pathway is specific to an effector family:
| Pathogen nutrition | Pathogen species | Plant disease and host plant species | Known effectors and their functions |
|---|---|---|---|
| Biotrophic | Blumeria graminis f. sp. hordei (Bgh) | Powdery mildew on barley | AVRA10 - recognized by the MLA10 R-protein from barley. [8] AVRK1 - recognized by the MLK1 R-protein from barley. [8] |
| Cladosporium fulvum | Leaf mould on tomato | Ecp6 - sequesters chitin, making less chitin available to bind PRRs. [9] Avr4 - binds to chitin oligomers in the fungal cell wall, protecting it from degradation by chitinases. [9] | |
| Ustilago maydis | Corn smut (maize) | Pep1; Pit2; Cmu1; Tin2; See1 | |
| Hemibiotrophic | Fusarium oxysporum f. sp. lycopersici | Tomato vascular wilt | Six1 (Avr3) - recognised by the R-protein I-3 from tomato, and when this happens local cell death is triggered as a defense mechanism. [10] Six3 (Avr2) - recognised by the R-protein I-2, triggering local cell death. [10] Six4 (Avr1) - suppresses I-2 and I-3-mediated cell death; in resistant tomato varieties Avr1 is recognised and neutralised by I and I-1. [10] Six6 - suppresses I-2 and I-3-mediated cell death. [10] |
| Leptosphaeria maculans | Blackleg disease on Brassica crops. [11] | AvrLm1; AvrLm2; AvrLm3 | |
| Magnaporthe oryzae | Rice blast disease | Cytoplasmic effectors: Avr-Pizt - interacts with the E3 ubiquitin ligase APIP6, which indirectly leads to reduced Reactive Oxygen Species (ROS) production and suppresses the expression of defence-related genes. [12] Pwl1, Pwl2, Bas1, Avr-Pita, MC69 Apoplastic effectors: Slp1 - binds to and sequesters chitin oligosaccharides. As a result, chitin is unavailable to bind to the host's chitin elicitor binding protein (CEBiP) and elicit PAMP-triggered defence responses. [13] BAS4, BAS113 | |
| Phytophthora infestans | Potato blight | AVR3a - cytoplasmic effector interacting with and stabilising the plant E3 ubiquitin ligase CMPG1. As a result CMPG1 is unable to get degraded and trigger cell death, allowing the pathogen to obtain nutrients from living host cells (biotrophy). AVRblb2 - a cytoplasmic effector preventing the secretion of a papain-like cysteine protease (C14) from the host, which would otherwise serve to degrade fungal effector proteins. [14] | |
| Necrotrophic | Pyrenophora tritici-repentis | Tan spot of wheat. [15] | PtrToxA; PtrToxB |
| Parastognospora nodorum | Septoria nodorum blotch in wheat. [16] | SnToxA; SnTox1; SnTox2; SnTox3; SnTox4; SnTox5; SnTox6; SnTox7; SnTox8 | |
| Cochliobolus heterostrophus | Southern corn leaf blight (maize) [17] | ChToxA - in maize varieties sensitive to ToxA it induces leaf necrosis in response to light. [18] | |
| Cochliobolus sativus | BsToxA | ||
| Corynespora cassiicola | Corynespora leaf fall disease in rubber trees [19] | Cassiicolin - disrupts the membranes of host plant cells, causing leaf necrosis. [19] | |
| Cochliobolus victoriae | victorin |
In biology, an effector is a general term that can refer to several types of molecules or cells depending on the context:
Phytoalexins are antimicrobial substances, some of which are antioxidative as well. They are defined, not by their having any particular chemical structure or character, but by the fact that they are defensively synthesized de novo by plants that produce the compounds rapidly at sites of pathogen infection. In general phytoalexins are broad spectrum inhibitors; they are chemically diverse, and different chemical classes of compounds are characteristic of particular plant taxa. Phytoalexins tend to fall into several chemical classes, including terpenoids, glycosteroids, and alkaloids; however the term applies to any phytochemicals that are induced by microbial infection.
Pathogen-associated molecular patterns (PAMPs) are small molecular motifs conserved within a class of microbes, but not present in the host. They are recognized by toll-like receptors (TLRs) and other pattern recognition receptors (PRRs) in both plants and animals. This allows the innate immune system to recognize pathogens and thus, protect the host from infection.
Pattern recognition receptors (PRRs) play a crucial role in the proper function of the innate immune system. PRRs are germline-encoded host sensors, which detect molecules typical for the pathogens. They are proteins expressed mainly by cells of the innate immune system, such as dendritic cells, macrophages, monocytes, neutrophils, as well as by epithelial cells, to identify two classes of molecules: pathogen-associated molecular patterns (PAMPs), which are associated with microbial pathogens, and damage-associated molecular patterns (DAMPs), which are associated with components of host's cells that are released during cell damage or death. They are also called primitive pattern recognition receptors because they evolved before other parts of the immune system, particularly before adaptive immunity. PRRs also mediate the initiation of antigen-specific adaptive immune response and release of inflammatory cytokines.
An appressorium is a specialized cell typical of many fungal plant pathogens that is used to infect host plants. It is a flattened, hyphal "pressing" organ, from which a minute infection peg grows and enters the host, using turgor pressure capable of punching through even Mylar.
The innate, or nonspecific, immune system is one of the two main immunity strategies in vertebrates. The innate immune system is an alternate defense strategy and is the dominant immune system response found in plants, fungi, insects, and primitive multicellular organisms.
Systemic acquired resistance (SAR) is a "whole-plant" resistance response that occurs following an earlier localized exposure to a pathogen. SAR is analogous to the innate immune system found in animals, and although there are many shared aspects between the two systems, it is thought to be a result of convergent evolution. The systemic acquired resistance response is dependent on the plant hormone, salicylic acid.
Hypersensitive response (HR) is a mechanism used by plants to prevent the spread of infection by microbial pathogens. HR is characterized by the rapid death of cells in the local region surrounding an infection and it serves to restrict the growth and spread of pathogens to other parts of the plant. It is analogous to the innate immune system found in animals, and commonly precedes a slower systemic response, which ultimately leads to systemic acquired resistance (SAR). HR can be observed in the vast majority of plant species and is induced by a wide range of plant pathogens such as oomycetes, viruses, fungi and even insects.
The gene-for-gene relationship is a concept in plant pathology that plants and their diseases each have single genes that interact with each other during an infection. It was proposed by Harold Henry Flor who was working with rust (Melampsora lini) of flax (Linum usitatissimum). Flor showed that the inheritance of both resistance in the host and parasite ability to cause disease is controlled by pairs of matching genes. One is a plant gene called the resistance (R) gene. The other is a parasite gene called the avirulence (Avr) gene. Plants producing a specific R gene product are resistant towards a pathogen that produces the corresponding Avr gene product. Gene-for-gene relationships are a widespread and very important aspect of plant disease resistance. Another example can be seen with Lactuca serriola versus Bremia lactucae.
Pseudomonas syringae is a rod-shaped, Gram-negative bacterium with polar flagella. As a plant pathogen, it can infect a wide range of species, and exists as over 50 different pathovars, all of which are available to researchers from international culture collections such as the NCPPB, ICMP, and others.
Damage-associated molecular patterns (DAMPs) are molecules within cells that are a component of the innate immune response released from damaged or dying cells due to trauma or an infection by a pathogen. They are also known as danger signals, and alarmins because they serve as warning signs to alert the organism to any damage or infection to its cells. DAMPs are endogenous danger signals that are discharged to the extracellular space in response to damage to the cell from mechanical trauma or a pathogen. Once a DAMP is released from the cell, it promotes a noninfectious inflammatory response by binding to a pattern recognition receptor. Inflammation is a key aspect of the innate immune response; it is used to help mitigate future damage to the organism by removing harmful invaders from the affected area and start the healing process. As an example, the cytokine IL-1α is a DAMP that originates within the nucleus of the cell which, once released to the extracellular space, binds to the PRR IL-1R, which in turn initiates an inflammatory response to the trauma or pathogen that initiated the release of IL-1α. In contrast to the noninfectious inflammatory response produced by DAMPs, pathogen-associated molecular patterns initiate and perpetuate the infectious pathogen-induced inflammatory response. Many DAMPs are nuclear or cytosolic proteins with defined intracellular function that are released outside the cell following tissue injury. This displacement from the intracellular space to the extracellular space moves the DAMPs from a reducing to an oxidizing environment, causing their functional denaturation, resulting in their loss of function. Outside of the aforementioned nuclear and cytosolic DAMPs, there are other DAMPs originated from different sources, such as mitochondria, granules, the extracellular matrix, the endoplasmic reticulum, and the plasma membrane.
Resistance genes (R-Genes) are genes in plant genomes that convey plant disease resistance against pathogens by producing R proteins. The main class of R-genes consist of a nucleotide binding domain (NB) and a leucine rich repeat (LRR) domain(s) and are often referred to as (NB-LRR) R-genes or NLRs. Generally, the NB domain binds either ATP/ADP or GTP/GDP. The LRR domain is often involved in protein-protein interactions as well as ligand binding. NB-LRR R-genes can be further subdivided into toll interleukin 1 receptor (TIR-NB-LRR) and coiled-coil (CC-NB-LRR).
Plant disease resistance protects plants from pathogens in two ways: by pre-formed structures and chemicals, and by infection-induced responses of the immune system. Relative to a susceptible plant, disease resistance is the reduction of pathogen growth on or in the plant, while the term disease tolerance describes plants that exhibit little disease damage despite substantial pathogen levels. Disease outcome is determined by the three-way interaction of the pathogen, the plant and the environmental conditions.
In plant biology, elicitors are extrinsic or foreign molecules often associated with plant pests, diseases or synergistic organisms. Elicitor molecules can attach to special receptor proteins located on plant cell membranes. These receptors are able to recognize the molecular pattern of elicitors and trigger intracellular defence signalling via the octadecanoid pathway. This response results in the enhanced synthesis of metabolites which reduce damage and increase resistance to pest, disease or environmental stress. This is an immune response called pattern triggered immunity (PTI).
Effector-triggered immunity (ETI) is one of the pathways, along with the pattern-triggered immunity (PTI) pathway, by which the innate immune system recognises pathogenic organisms and elicits a protective immune response. ETI is elicited when an effector protein secreted by a pathogen into the host cell is successfully recognised by the host. Alternatively, effector-triggered susceptibility (ETS) can occur if an effector protein can block the immune response triggered by pattern recognition receptors (PRR) and evade immunity, allowing the pathogen to propagate in the host.
Leucine-rich repeat receptor like protein kinase are plant cell membrane localized Leucine-rich repeat (LRR) receptor kinase that play critical roles in plant innate immunity. Plants have evolved intricate immunity mechanism to combat against pathogen infection by recognizing Pathogen Associated Molecular Patterns (PAMP) and endogenous Damage Associated Molecular Patterns (DAMP). PEPR 1 considered as the first known DAMP receptor of Arabidopsis.
Aspergillus giganteus is a species of fungus in the genus Aspergillus that grows as a mold. It was first described in 1901 by Wehmer, and is one of six Aspergillus species from the Clavati section of the subgenus Fumigati. Its closest taxonomic relatives are Aspergillus rhizopodus and Aspergillus longivescia.
Hemibiotrophs are the spectrum of plant pathogens, including bacteria, oomycete and a group of plant pathogenic fungi that keep its host alive while establishing itself within the host tissue, taking up the nutrients with brief biotrophic-like phase. It then, in later stages of infection switches to a necrotrophic life-style, where it rampantly kills the host cells, deriving its nutrients from the dead tissues.
Xanthoferrin is an α-hydroxycarboxylate-type of siderophore produced by xanthomonads. Xanthomonas spp. secrete xanthoferrin to chelate iron under low-iron conditions. The xanthoferrin siderophore mediated iron uptake supports bacterial growth under iron-restricted environment.
Diane G. O. Saunders is a British biologist and group leader at the John Innes Centre and an Honorary Professor in the School of Biological Sciences at the University of East Anglia. Her research investigates plant pathogens that pose a threat to agriculture. She was awarded the Rosalind Franklin Award by the Royal Society in 2022.