Abstract
The "brain-eating amoeba"
dwells in ponds where it normally feeds on bacteria, but if it enters the brain it can cause a deadly infection. To establish infection,
must migrate through different environments-along olfactory axons, through openings in the cribriform plate, and within brain tissue-yet how it does so remains unknown. As a model for
migration within these environments, we examine how its non-pathogenic relative,
, navigates environments of distinct geometries. We show that
uses both actin-rich protrusions and membrane blebs to crawl across or between flat surfaces. We also explore how
interact with narrow channels and find that, unlike
amoebae that we show frequently disengage from channel interfaces,
amoebae probe channels until they enter. Once inside,
crawls quickly (>50 μm/min) and unidirectionally over long distances (>1 mm) using only bleb-based motility. We also introduced
to granular hydrogel matrices that mimic pond sediments and found that cells readily enter and migrate through these three-dimensional matrices using both blebs and lamellar protrusions. Although cells in matrices showed lower persistence at short timescales, longer time scales correlate with increased persistence, suggesting
cells may retain memory of past orientation. We propose that pond life may select for three behaviors that prime
for pathogenesis: memory-guided motility that would facilitate exploration of sinus cavities, confinement-seeking ("claustrophilia") that would promote entry into narrow passages along olfactory axons, and fast bleb-based migration that would allow rapid transit along axons to the brain.
The "brain-eating amoeba"
causes a devastating brain infection with a ∼95% fatality rate, yet how these normally harmless pond-dwellers invade the human brain remains mysterious. Using the model species
, we show that
amoebae exhibit three key behaviors: they retain directional memory during exploration, actively enter confined spaces, and crawl rapidly and persistently through narrow channels for millimeter-scale distances. We propose these behaviors are adaptations for hunting bacteria in pond sediments that inadvertently enable pathogenesis-directional memory facilitates sinus exploration, confinement-seeking draws amoebae into spaces between olfactory axons, and persistent channel migration enables rapid transit to the brain.