Protein Secretion and Pathogen Interactions in Fungal Systems

Fungal organisms deploy a sophisticated secretory network to export proteins that facilitate nutrient acquisition, host colonisation and evasion of immune defences. Central to this process is the classical secretory pathway, in which nascent polypeptides bearing N-terminal signal peptides are translocated into the endoplasmic reticulum, modified in the Golgi apparatus and dispatched via vesicular trafficking to the extracellular milieu or directly into host cells. Alongside this canonical route, fungi employ non-classical mechanisms—including extracellular vesicles and unconventional secretion—to deliver effectors, enzymes and small molecules into the apoplast or across host cellular membranes. These secreted factors modulate host signalling, degrade structural barriers and suppress defence responses, underpinning both biotrophic and necrotrophic lifestyles. The fungal secretome thus represents a dynamic interface between pathogen and host, with broad implications for agriculture, medicine and biotechnology. Advances in high-throughput proteomics, transcriptomics and computational prediction have greatly expanded our understanding of the repertoire and regulation of secreted proteins, revealing novel virulence determinants and offering new targets for disease control and crop protection.

Research from Nature Portfolio

Recent studies have demonstrated the power of machine-learning frameworks to enhance signal peptide detection across diverse fungal lineages. A next-generation predictor now recognises all known classes of signal peptides, enabling accurate annotation of secreted proteins from genome and metagenome datasets and uncovering previously cryptic effector repertoires. In parallel, a specialised tool for fungal effectors has been developed to predict subcellular targeting in host cells, revealing that many rust and smut fungi secrete proteins that mimic plant transit peptides to enter chloroplasts and nuclei. This approach has led to the experimental validation of novel effectors that exploit host organellar import pathways, shedding light on how fungal pathogens subvert key aspects of plant cell biology.

Protein Secretion and Pathogen Interactions in Fungal Systems publication trend

The graph below shows the total number of articles in protein secretion and pathogen interactions in fungal systems across all publications each year (not limited to Nature Index journals).

Technical terms

Signal peptide: Short N-terminal sequence that directs proteins into the endoplasmic reticulum for secretion.

Secretome: The full complement of proteins secreted by an organism.

Effector protein: A secreted molecule that manipulates host cell structure or immunity to promote infection.

Exocytosis: Vesicle-mediated fusion of secretory compartments with the plasma membrane, releasing cargo extracellularly.

Apoplast: The extracellular space in plant tissues, including cell walls and intercellular spaces, where pathogen–host interactions often occur.

References

1. SignalP 6.0 predicts all five types of signal peptides using protein language models. Nature Biotechnology (2022).
2. LOCALIZER: subcellular localization prediction of both plant and effector proteins in the plant cell. Scientific Reports (2017).
3. Computational Prediction of Effector Proteins in Fungi: Opportunities and Challenges. Frontiers in Plant Science (2016).
4. PHI-base in 2022: a multi-species phenotype database for Pathogen–Host Interactions. Nucleic Acids Research (2021).