Elsevier

Current Opinion in Microbiology

Volume 23, February 2015, Pages 14-22
Current Opinion in Microbiology

Targeting of plant pattern recognition receptor-triggered immunity by bacterial type-III secretion system effectors

https://doi.org/10.1016/j.mib.2014.10.009Get rights and content

Highlights

  • Type-III effectors (T3Es) suppress plant immunity using multiple strategies.

  • PRR-triggered immunity is redundantly targeted by multiple T3Es from a single bacterial strain.

  • A single T3E can have multiple plant targets.

  • A given immune component can be targeted by multiple T3Es.

  • The study of T3Es reveals important immune components and unique biochemical processes.

During infection, microbes are detected by surface-localized pattern recognition receptors (PRRs), leading to an innate immune response that prevents microbial ingress. Therefore, successful pathogens must evade or inhibit PRR-triggered immunity to cause disease. In the past decade, a number of type-III secretion system effector (T3Es) proteins from plant pathogenic bacteria have been shown to suppress this layer of innate immunity. More recently, the detailed mechanisms of action have been defined for several of these effectors. Interestingly, effectors display a wide array of virulence targets, being able to prevent activation of immune receptors and to hijack immune signaling pathways. Besides being a fascinating example of pathogen-host co-evolution, effectors have also emerged as valuable tools to dissect important biological processes in host cells.

Introduction

Major bacterial pathogens of plants include members of the Pseudomonas, Xanthomonas, Ralstonia, Agrobacterium and Pectobacterium genera, amongst others. As all would-be pathogens, they face efficient innate immune responses when first coming into contact with plant cells. Surface-localized pattern recognition receptors (PRRs) ensure initial perception of this infectious non-self [1, 2]. Plant PRRs can perceive conserved bacterial molecules, usually termed pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs), such as bacterial flagellin, elongation factor Tu (EF-Tu), peptidoglycan (PGN) or lipopolysaccharides [3, 4].

Plant PRRs are either plasma membrane-resident receptor kinases (RKs) or receptor-like proteins (RLPs) [3, 4]. Plant PRRs exist within dynamic protein complexes composed of PRRs themselves, co-receptors, regulatory proteins, and components directly involved in intracellular signaling [3, 5]. Upon PAMP perception, the activation of different PRR complexes leads to the phosphorylation and activation of cytoplasmic receptor-like cytoplasmic kinases (RLCKs) [5, 6]. Downstream immune responses include the activation of mitogen-activated protein kinases (MAPKs) and calcium-dependent protein kinases (CDPKs), the rapid generation of reactive oxygen species (ROS), the expression of immune-related genes, and the deposition of callose at the cell wall [7, 8]. Collectively, these responses culminate in PRR- or PAMP-triggered immunity (PTI), which is sufficient to halt the ingress or growth of most microbes.

Therefore, successful pathogens must either evade or actively suppress this important layer of plant innate immunity in order to cause disease. Several Gram-negative bacterial pathogens do so by using the type III-secretion system (T3SS), which resembles a molecular syringe that injects proteins directly inside the host cell [9]. These proteins are usually referred to as type III effectors (T3Es), and promote bacterial infection by manipulating host cell functions, including immunity. The relevance of this secretion system in the overall virulence of plant pathogenic bacteria is best proven by the near-complete loss of infectivity of strains unable to secrete T3Es [10]. However, resistant plants employ intracellular immune receptors, most often of the nucleotide-binding domain-LRR receptor (NLR) type, which directly or indirectly recognize T3Es, thereby inducing effector-triggered immunity (ETI; [2]. Plant pathogenic bacteria also employ additional virulence strategies, such as evasion of PAMP detection or production of toxins, among others [7, 11].

Here, we will review the different strategies evolved by T3Es from plant pathogenic bacteria to impede PTI by directly targeting PRR themselves, their biogenesis, or key signaling components acting downstream of PRR activation. We will mainly focus on T3Es for which molecular plant targets are known. Therefore, we apologize to colleagues whose work on other effectors is not covered.

Section snippets

Effectors that target de novo PRR biogenesis

In response to PAMP perception, transcripts of a large number of PRRs are rapidly up-regulated [12, 13, 14]. This may represent an amplification mechanism, but also could serve to replenish the plasma membrane with ligand-free PRRs for subsequent waves of PAMP recognition and PRR activation. The targeting of this de novo PRR biogenesis could therefore represent a virulence strategy to block the establishment of sustained PTI during infection (Figure 1).

Interestingly, the T3E HopU1 from

Effectors that target directly PRRs and their co-receptors

Several T3Es have been found to target PRRs directly, causing their degradation and/or the inhibition of their PAMP-induced activation (Figure 2).

An example of T3E that exerts both functions is AvrPtoB, which is a multi-domain protein with orthologs in several P. syringae pathovars. AvrPtoB uses a C-terminal E3 ligase domain to ubiquitinate and induce the proteasome-mediated degradation of PRRs, such as FLS2, and the LysM-RK CERK1, which is involved in PGN perception [23, 24, 25]. Moreover,

Effectors that target PRR-associated cytoplasmic kinases

The T3E AvrPphB from Pph 1448A is a cysteine protease related to Yersinia pestis YopT [41]. It can inhibit PTI signaling by cleaving multiple members of the BIK1 family of RLCKs that are direct substrates of multiple PRR complexes [5, 42] (Figure 2). Interestingly, plants harboring the intracellular immune receptor RPS5, an NLR protein, are able to detect AvrPphB-mediated cleavage of one of those RLCKs, PBS1, to initiate ETI [43]. This is good illustration that, while T3Es are key virulence

Effectors that target MAP kinases

HopAI1 from Pto DC3000 inactivates MPK3, MPK4 and MPK6 in an irreversible manner [50, 51]. This is achieved through a phosphothreonine lyase activity, similar to what is observed in the Shigella flexneri T3E OspF, which targets animal MAPKs [50, 52]. However, in plants carrying the NLR SUMM2, inactivation of MPK4 by HopAI1 results in ETI [51]. The fact that both RLCKs and MAPKs are guarded by resistance proteins support the notion that they constitute key components of plant immune signaling

Effectors that target vesicle trafficking to suppress PTI

Vesicle trafficking is an important cellular function. Regarding plant immune functions, vesicle trafficking is necessary for the transport of immune receptors and associated proteins, and for the secretion of immune related molecules and antimicrobial compounds upon pathogen detection [62].

HopM1 from Pto DC3000 interacts with and induces the degradation of the ADP ribosylation factor (ARF) guanine nucleotide exchange factor (GEF) protein AtMIN7 in a proteasome-dependent manner [63]. AtMIN7

Effectors that target 14-3-3 proteins to suppress PTI

Consistent with the importance of protein phosphorylation for immune signaling [5], 14-3-3 proteins are emerging as important players in plant immunity [69, 70, 71]. 14-3-3 proteins bind to specific motifs containing phosphorylated serine or threonine residues, regulating the function of target proteins by several different mechanisms [72]. Several T3Es interact with 14-3-3 proteins, which could serve as a mechanism to disrupt immunity-associated 14-3-3 functions, or a way to exploit host

Concluding remarks

The detailed study of T3Es, mainly from Pseudomonas and Xanthomonas species, has revealed that one major function of these effectors is to actively suppress PTI by directly targeting key components of this important layer of immune recognition. As such, T3Es (and virulence effectors in general) can be considered as very useful biological tools to dissect key biological processes and may also reveal novel activities evolved to achieve their virulence functions [77, 78].

A number of general

References and recommended reading

Papers of particular interest, published within the period of review, have been highlighted as:

  • • of special interest

  • •• of outstanding interest

Acknowledgements

Research in the Zipfel laboratory is funded by the Gatsby Foundation and the European Research Council. We thank all members of the Zipfel laboratory for helpful discussions. We apologize to colleagues whose work could not be cited due to space limits.

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