Abscisic Acid as Pathogen Effector and Immune Regulator

Abstract

Abscisic acid (ABA) is a sesquiterpene signaling molecule produced in all kingdoms of life. To date, the best known functions of ABA are derived from its role as a major phytohormone in plant abiotic stress resistance. Different organisms have developed different biosynthesis and signal transduction pathways related to ABA. Despite this, there are also intriguing common themes where ABA often suppresses host immune responses and is utilized by pathogens as an effector molecule. ABA also seems to play an important role in compatible mutualistic interactions such as mycorrhiza and rhizosphere bacteria with plants, and possibly also the animal gut microbiome. The frequent use of ABA in inter-species communication could be a possible reason for the wide distribution and re-invention of ABA as a signaling molecule in different organisms. In humans and animal models, it has been shown that ABA treatment or nutrient-derived ABA is beneficial in inflammatory diseases like colitis and type 2 diabetes, which confer potential to ABA as an interesting nutraceutical or pharmacognostic drug. The anti-inflammatory activity, cellular metabolic reprogramming, and other beneficial physiological and psychological effects of ABA treatment in humans and animal models has sparked an interest in this molecule and its signaling pathway as a novel pharmacological target. In contrast to plants, however, very little is known about the ABA biosynthesis and signaling in other organisms. Genes, tools and knowledge about ABA from plant sciences and studies of phytopathogenic fungi might benefit biomedical studies on the physiological role of endogenously generated ABA in humans.

Keywords: comparative biology; host-microbe interactions; immunity; inflammation; metabolic engineering; natural product chemistry; signal transduction; systems biology.

Figure 1

A simplified overview of the direct ABA biosynthesis in fungi and the indirect biosynthesis in plants. Yellow background indicates cytosolic compartment, and green background the chloroplast compartment. For more detailed biosynthetic pathways, see Siewers et al. (2006) for the direct pathway in fungi and Finkelstein (2013) for the indirect pathway in plants. Molecular structures in scalable vector graphics (SVG) format were obtained from Wikipedia (https://en.wikipedia.org) on 2017-02-08, and the images were licensed “public domain” by the original authors.

Figure 2

(A) Phylogeny of Botrytis P450 ABA biosynthesis proteins BcABA1 and BcABA2 (red) compared to all human P450 proteins (black). (B) Phylogeny of Botrytis BcABA4 biosynthesis protein (red) compared to all human carbonyl reductase family members (black).

Figure 3

A simplified overview of synergistic and antagonistic interactions between plant stress resistance hormone signaling pathways. The simplified overview does not accurately describe the plant hormone involvement in all plant pathosystems, where variations may occur.

Figure 4

An overview of proposed signaling pathways for ABA in animal cells. Regulation of intracellular free ABA homeostasis by biosynthesis/catabolism, export/import and conjugation/deconjugation are currently unknown in animals. Different ABA receptors have been proposed for ABA, such as the bitter taste receptor (T2R4), LANCL2, retinoic acid receptors (RARs), and HSP70 (GRP78).