Host-Pathogen Interactions in Amoeboid Systems

Amoebae of the Dictyostelia and Acanthamoeba lineages have emerged as powerful models for dissecting the cellular interplay between protozoan hosts and intracellular pathogens. These free-living phagocytes employ phagocytosis and macropinocytosis to internalise prey and pathogens, engaging a suite of membrane remodelling and defence pathways to contain, kill or tolerate invaders. Key processes include the maturation of pathogen-containing vacuoles into hostile compartments, the recruitment of reactive oxygen species and degradative enzymes, and the activation of selective autophagy or xenophagy to eliminate cytosolic microbes. Conversely, pathogens such as Mycobacterium marinum and various bacteria have evolved sophisticated mechanisms to damage phagosomal membranes, subvert host cytoskeletal motors, or modulate ubiquitin-dependent signalling to escape into the cytosol or hijack host machinery. Studies leveraging genetic tractability and live-cell imaging in amoeboid systems have uncovered conserved elements of cell-autonomous immunity, revealed novel damage-sensing factors, and highlighted the dynamic tug-of-war at the host–pathogen interface. Beyond fundamental insights into eukaryotic cell biology, this work carries global significance for understanding the evolution of innate immunity and for identifying targets to counteract intracellular pathogens in human health and environmental contexts.

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Recent work in eLife has identified the E3 ubiquitin ligase TrafE as a pivotal sensor of endolysosomal damage during infection by Mycobacterium marinum in Dictyostelium discoideum. TrafE is recruited to disrupted compartments, where it bridges ESCRT (endosomal sorting complex required for transport) and autophagy machineries, orchestrating membrane repair or removal of damaged vacuoles and restricting bacterial proliferation.

In mBio, advanced imaging studies have revealed that the endoplasmic reticulum contributes directly to the repair of mycobacterial vacuole membranes in D. discoideum. The ER–Golgi lipid transfer protein OSBP8 delivers lipids to lesions in the mycobacteria-containing vacuole, preserving lysosomal integrity and limiting pathogen escape and replication.

A recent genome-wide fitness analysis in mSystems has illuminated the genetic requirements for Mycobacterium marinum survival within both D. discoideum and murine microglial cells. Transposon-sequencing identified core pathways—lipid metabolism, DNA repair, type VII secretion and the Mce1 lipid transport system—that underpin virulence and adaptation within amoeboid hosts, uncovering conserved strategies of intracellular persistence and informing potential anti-virulence interventions.

Host-Pathogen Interactions in Amoeboid Systems publication trend

The graph below shows the total number of articles in host-pathogen interactions in amoeboid systems across all publications each year (not limited to Nature Index journals).

Technical terms

Phagocytosis: Engulfment of particles by cell membrane invagination to form an intracellular vesicle.

Macropinocytosis: Uptake of extracellular fluid and solutes via large, actin-driven membrane ruffles.

Vacuole: A membrane-bound compartment that houses ingested material or pathogens within a host cell.

ESCRT: Endosomal sorting complex required for transport, a set of proteins that mediate membrane remodelling and repair.

Autophagy: Cellular degradation pathway involving the formation of double-membrane autophagosomes to sequester and recycle cytosolic material.

Xenophagy: Selective form of autophagy targeting intracellular pathogens for destruction.

E3 ubiquitin ligase: Enzyme that tags proteins or membranes with ubiquitin to signal for degradation or membrane repair.

References

1. A TRAF-like E3 ubiquitin ligase TrafE coordinates ESCRT and autophagy in endolysosomal damage response and cell-autonomous immunity to Mycobacterium marinum. eLife (2023).
2. ER-dependent membrane repair of mycobacteria-induced vacuole damage. mBio (2023).
3. Temporal genome-wide fitness analysis of Mycobacterium marinum during infection reveals the genetic requirement for virulence and survival in amoebae and microglial cells. mSystems (2024).