Acetylation enables a dual-targeting fungal effector to inhibit insect immunity and development
- 1Anhui Provincial Key Laboratory of Biological Control, Anhui Agricultural University, Hefei, China.
- 2Hefei Forestry Protection Center, Hefei, China.
Abstract
Pathogenic microbes deploy secreted effectors to subvert host immunity and physiology across kingdom boundaries, yet the molecular mechanisms that maintain effector competence during this transition remain poorly defined. Here, we identify MrNIS1, an effector from the insect-pathogenic fungus Metarhizium robertsii whose stability and secretion are governed by K24 acetylation through physical association with the acetyltransferase MrKAT1 and the deacetylase MrSIR2. Once inside the insect, MrNIS1 acts as a dual-targeting effector to disrupt distinct physiological pathways. It binds the serine protease SPS to block prophenoloxidase activation, thereby suppressing melanization-based immunity. MrNIS1 interacts with the evolutionarily conserved cholesterol transporter ERP, disrupting ecdysteroid biosynthesis and leading to impaired larval growth and cuticle synthesis. This MrNIS1-ERP interaction is functionally conserved across Lepidoptera, Coleoptera, and Diptera. Furthermore, heterologous expression in Beauveria bassiana demonstrates that the KAT1/SIR2 regulatory system is conserved across fungal species, where MrNIS1 acts as a portable virulence module to significantly enhance pathogen efficacy. Our findings reveal that lysine acetylation serves as a molecular switch that preserves effector competence during cross-kingdom transit, enabling the simultaneous targeting of multiple host physiological processes. These results elucidate a conserved strategy of fungal pathogenesis and identify potential targets for the improvement of microbial biocontrol agents. Author summary: Fungal pathogens secrete effectors to manipulate hosts, but how these weapons remain stable during transmission is unclear. Our study reveals that lysine acetylation of an insect-pathogenic fungal effector ensures its stability, delivery, and function inside hosts. Once there, it simultaneously disrupts immune defense and hormone signaling—blocking both protective melanization and larval development. This regulatory system can be transferred to other fungi to enhance their virulence. These findings uncover a molecular mechanism preserving effector competence across kingdoms and offer a strategy to improve biological pest control.
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BibTeX
@article{wang2026acetylation,
title = {{Acetylation enables a dual-targeting fungal effector to inhibit insect immunity and development}},
author = {Yulong Wang and Ying Dong and Yang Zhang and Siying Wu and Deshui Yu and Guang Yang and Shuqian Gao and Yang Yang and Shihao Dong and Li Qin and Bo Huang},
journal = {PLOS Pathogens},
year = {2026},
month = oct,
doi = {10.1371/journal.ppat.1014680},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014680},
note = {CC BY},
}
RIS
TY - JOUR
TI - Acetylation enables a dual-targeting fungal effector to inhibit insect immunity and development
AU - Yulong Wang
AU - Ying Dong
AU - Yang Zhang
AU - Siying Wu
AU - Deshui Yu
AU - Guang Yang
AU - Shuqian Gao
AU - Yang Yang
AU - Shihao Dong
AU - Li Qin
AU - Bo Huang
PY - 2026
DA - 2026/10/05
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014680
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014680
AB - Pathogenic microbes deploy secreted effectors to subvert host immunity and physiology across kingdom boundaries, yet the molecular mechanisms that maintain effector competence during this transition remain poorly defined. Here, we identify MrNIS1, an effector from the insect-pathogenic fungus Metarhizium robertsii whose stability and secretion are governed by K24 acetylation through physical association with the acetyltransferase MrKAT1 and the deacetylase MrSIR2. Once inside the insect, MrNIS1 acts as a dual-targeting effector to disrupt distinct physiological pathways. It binds the serine protease SPS to block prophenoloxidase activation, thereby suppressing melanization-based immunity. MrNIS1 interacts with the evolutionarily conserved cholesterol transporter ERP, disrupting ecdysteroid biosynthesis and leading to impaired larval growth and cuticle synthesis. This MrNIS1-ERP interaction is functionally conserved across Lepidoptera, Coleoptera, and Diptera. Furthermore, heterologous expression in Beauveria bassiana demonstrates that the KAT1/SIR2 regulatory system is conserved across fungal species, where MrNIS1 acts as a portable virulence module to significantly enhance pathogen efficacy. Our findings reveal that lysine acetylation serves as a molecular switch that preserves effector competence during cross-kingdom transit, enabling the simultaneous targeting of multiple host physiological processes. These results elucidate a conserved strategy of fungal pathogenesis and identify potential targets for the improvement of microbial biocontrol agents. Author summary: Fungal pathogens secrete effectors to manipulate hosts, but how these weapons remain stable during transmission is unclear. Our study reveals that lysine acetylation of an insect-pathogenic fungal effector ensures its stability, delivery, and function inside hosts. Once there, it simultaneously disrupts immune defense and hormone signaling—blocking both protective melanization and larval development. This regulatory system can be transferred to other fungi to enhance their virulence. These findings uncover a molecular mechanism preserving effector competence across kingdoms and offer a strategy to improve biological pest control.
SN - 1553-7374
SN - 1553-7366
ER -