Chemical Biology of Host-Microbe Interaction – Unraveling Cellular Re-Programming Underlying Fungal Virulence and Host Immunity

ost-microbe interaction is typically best described by the fine-tuned and intricate cellular communication between the partners. Microbes have evolved to synthesize natural products that often mimic host cell determinants and are capable of modulating host cellular functions and/or immunity. The study of the chemical and cell biology of host-pathogen interactions is emerging as a key research area of animal and plant disease control in the post-genomic and metabolomic era. In a model patho-system of rice-blast disease caused by a fungal athogen Magnaporthe oryzae, we identified a pathogenicity gene cluster encoding genes essential for the development of the specialized infection structures (appressoria) and modulation of host immunity. Previously, we showed that M. oryzae produces a digoxin-like endogenous steroidal glycoside (ATS), which plays an important role in regulating ion homeostasis and actin cytoskeleton during pathogenic development and whose timely efflux by an ABC3 transporter is essential for host invasion. While excess accumulation of ATS in the absence of ABC3 function (abc3Δ) is inhibitory to the fungal pathogen, it also has an ability to induce host immunity. Lately, we identified a novel fungal monooxygenase (Abm), which converts endogenous jasmonic acid (JA; analog of plant hormone) into 12-hydroxyjasmonic acid (12OH-JA), and shares the aforementioned gene cluster with the ABC3 transporter. Interestingly, 12OH-JA is secreted out of the appressoria to inactivate early defense response during host penetration. Strikingly, Abm itself is secreted post invasion and converts host JA into 12OH-JA to facilitate biotrophic growth and establishment. Importantly, loss of Abm (abmΔ) in M. oryzae leads to excess methylated JA, which induces host defense and blocks fungal invasive growth. While this study sheds light on the chemical arms race between a plant and its pathogen, it promises to give insight into the cellular processes themselves.