Vacuolar recruitment of retromer by a SNARE complex enables infection-related trafficking in rice blast.

The retromer complex is a conserved sorting machinery that maintains cellular protein homeostasis by transporting vesicles containing cargo proteins to defined destinations. It is known to sort proteins at the vacuole membranes for retrograde trafficking, preventing their degradation in the vacuole. However, the detailed mechanism of retromer recruitment to the vacuole membrane has not yet been elucidated. Here, we show that the vacuolar SNARE complex MoPep12-MoVti1-MoVam7-MoYkt6 regulates retromer-mediated vesicle trafficking by recruiting the retromer to the vacuole membrane, which promotes host invasion in Magnaporthe oryzae. Such recruitment is also essential for the retrieval of the autophagy regulator MoAtg8 and enables appressorium-mediated host penetration. Furthermore, the vacuolar SNARE subunits are involved in suppressing the host defense response by regulating the deployment of retromer-MoSnc1-mediated effector secretion. Altogether, our results provide insights into the mechanism of vacuolar SNAREs-dependent retromer recruitment which is necessary for pathogenicity-related membrane trafficking events in the rice blast fungus.

Coacervate-Based Instant and Repeatable Underwater Adhesive with Anticancer and Antibacterial Properties.

Underwater adhesion is a great challenge for the development of adhesives as the attractive interfacial intermolecular interactions are usually weakened by the surface hydration layer. The coacervation process of sessile organisms like marine mussels and sandcastle worms has inspired substantial research interest in the fabrication of long-lasting underwater adhesives, but they generally suffer from time-consuming curing triggered by surrounding environmental changes and cannot reserve the adhesiveness once damaged. Herein, an instant and repeatable underwater adhesive was developed based on the coacervation of tannic acid (TA) and poly(ethylene glycol)77-b-poly(propylene glycol)29-b-poly(ethylene glycol)77 (PEG-PPG-PEG, F68), which was driven by hydrogen-bonding interaction, and the hydrophobic cores of F68 micelles offered an additional cross-linking to enhance the mechanical properties. The TA-F68 coacervates could be facilely painted on different substrates, exhibiting robust and instant underwater adhesion (with adhesion strength up to 1.1 MPa on porcine skin) and excellent repeatability (at least 1000 cycles), superior to the previously reported coacervates. Due to the biological activities of TA, the underwater adhesive displayed innate anticancer and antibacterial properties against different types of cancer cells and bacteria, showing great potential for diverse biomedical applications, such as injectable drug carriers, tissue glues, and wound dressings.

Trehalose Phosphate Synthase Complex-Mediated Regulation of Trehalose 6-Phosphate Homeostasis Is Critical for Development and Pathogenesis in Magnaporthe oryzae.

Trehalose biosynthesis pathway is a potential target for antifungal drug development, and trehalose 6-phosphate (T6P) accumulation is widely known to have toxic effects on cells. However, how organisms maintain a safe T6P level and cope with its cytotoxicity effects when accumulated have not been reported. Herein, we unveil the mechanism by which the rice blast fungus Magnaporthe oryzae avoids T6P accumulation and the genetic and physiological adjustments it undergoes to self-adjust the metabolite level when it is unavoidably accumulated. We found that T6P accumulation leads to defects in fugal development and pathogenicity. The accumulated T6P impairs cell wall assembly by disrupting actin organization. The disorganization of actin impairs the distribution of chitin synthases, thereby disrupting cell wall polymer distribution. Additionally, accumulation of T6P compromise energy metabolism. M. oryzae was able to overcome the effects of T6P accumulation by self-mutation of its MoTPS3 gene at two different mutation sites. We further show that mutation of MoTPS3 suppresses MoTps1 activity to reduce the intracellular level of T6P and partially restore ΔMotps2 defects. Overall, our results provide insights into the cytotoxicity effects of T6P accumulation and uncover a spontaneous mutation strategy to rebalance accumulated T6P in M. oryzae. IMPORTANCE M. oryzae, the causative agent of the rice blast disease, threatens rice production worldwide. Our results revealed that T6P accumulation, caused by the disruption of MoTPS2, has toxic effects on fugal development and pathogenesis in M. oryzae. The accumulated T6P impairs the distribution of cell wall polymers via actin organization and therefore disrupts cell wall structure. M. oryzae uses a spontaneous mutation to restore T6P cytotoxicity. Seven spontaneous mutation sites were found, and a mutation in MoTPS3 was further identified. The spontaneous mutation in MoTPS3 can partially rescue ΔMotps2 defects by suppressing MoTps1 activity to alleviate T6P cytotoxicity. This study provides clear evidence for better understanding of T6P cytotoxicity and how the fungus protects itself from T6P's toxic effects when it has accumulated to severely high levels.