The discovery of the BABA receptor: scientific implications and application potential

A significant proportion of global crop production is annually lost to pests and diseases (Savary et al., 2012). While pesticides help to reduce these losses, there is growing concern about pesticide resistance and their impacts on health and environment. Integrated Pest Management (IPM) aims to reduce pesticide usage through a combination of different strategies, including resistant crop cultivars, monitoring disease status, and mechanical and biological control (Birch et al., 2011; Chandler et al., 2011). A potentially novel IPM tool is plant priming agents: stimuli that sensitize the plant’s immune system for augmented activation against future pathogen/herbivore attacks. Because priming leads to augmented activation of multi-genic defense mechanisms (Ton et al., 2006; Ahmad et al., 2010), the resulting resistance has the potential to be more durable than protection by single resistance (R-) genes. Despite this advantage, priming agents are not widely used in agriculture, partly because they often do not provide the same level of protection as conventional pesticides and Rgenes (Walters et al., 2013). However, the advancement of IPM has spurred increased interest in exploiting priming agents in sustainable crop protection schemes. Arguably the most effective priming agent is β-aminobutyric acid (BABA). This non-protein amino acid primes defense reactions that are controlled by salicylic acid (SA)-dependent and -independent signaling pathways (Zimmerli et al., 2000; Ton et al., 2005), conferring protection in different plant species against an exceptionally broad spectrum of stresses, including microbial pathogens, herbivores, and abiotic stresses (Jakab et al., 2001; Cohen, 2002). Unfortunately, BABA also has an undesirable side effect: it reduces plant growth (Wu et al., 2010). While this growth penalty is outweighed by its protective effects in environments with high disease pressure, it can be quite severe at higher doses under disease-free conditions (Van Hulten et al., 2006). Until now, understanding of the molecular mechanisms underpinning the tradeoff between BABA-IR and BABA-induced growth repression was limited by insufficient knowledge of how this chemical is perceived in plants. A recent study, however, has provided new insight in this matter (Luna et al., 2014). A screen for Arabidopsis mutants in BABA-IR against the biotrophic oomycete Hyaloperonospora arabidopsidis led to the identification of the Impaired in BABA-induced Immunity 1 (IBI1) gene, encoding an aspartyl-tRNA synthetase (AspRS). Unlike previously identified genes controlling either SAdependent, or SA-independent BABA-IR (Ton et al., 2005), the ibi1-1 mutation was found to block both priming responses to BABA, indicating unilateral control of BABA-induced resistance by IBI1. The stereochemical similarity between the amino acid substrate of IBI1 (Laspartate; L-asp) and the active enantiomer of BABA (R-BABA) suggested that IBI1 might function as the BABA receptor. This hypothesis was supported by several indirect lines of evidence; apart from loss of BABA-IR by independent mutations in IBI1, computational models of BABA-binding to AspRS enzymes indicated high-affinity binding of R-BABA in a similar molecular orientation as L-asp, while treatment with active R-BABA caused cellular L-asp accumulation. Further evidence for receptor functionality by IBI1 came from the in planta demonstration that R-BABA physically binds to IBI1. It was concluded that R-BABA binds the L-aspbinding domain of IBI1, thereby disrupting canonical AspRS activity and priming the protein for non-canonical defense activity. This model also predicts that RBABA increases uncharged tRNAasp accumulation. Across eukaryotes, uncharged tRNA serves as a conserved signal for metabolic imbalance by activating the protein kinase GCN2 (Dong et al., 2000; Dever and Hinnebusch, 2005), which in turn inhibits translational activity via phosphorylation of eukaryotic translation initiation factor eIF2α (Wek et al., 2006; Li et al., 2013). Evidence that this stress pathway is activated by BABA came from the demonstration that stressinducing concentrations of BABA activate GCN2-dependent eIF2α phosphorylation. Moreover, the gcn2-1 mutant of Arabidopsis was strongly reduced in BABA-induced growth inhibition, while it remained unaffected in BABA-induced