The intricate complexity, at the molecular and cellular levels, of the processes leading to the development of
amyloid proteinopathies is somehow counterbalanced by their common, universal structural basis. The later has fueled the quest for suitable model systems to study
protein amyloidosis under quasi-physiological conditions in vitro and in simpler organisms in vivo. Yeast
prions have provided several of such model systems, yielding invaluable insights on
amyloid structure, dynamics and transmission. However, yeast
prions, unlike mammalian PrP, do not elicit any
proteinopathy. We have recently reported that engineering RepA-WH1, a
bacterial DNA-toggled
protein conformational switch (dWH1 → mWH1) sharing some analogies with
nucleic acid-promoted PrPC → PrPSc replication, enables control on
protein amyloidogenesis in vitro. Furthermore, RepA-WH1 gives way to a non-infectious, vertically-transmissible (from mother to daughter cells)
amyloid proteinopathy in Escherichia coli. RepA-WH1
amyloid aggregates efficiently promote aging in bacteria, which exhibit a drastic lengthening in generation time, a limited number of division cycles and reduced fitness. The RepA-WH1 prionoid opens a direct means to untangle the general pathway(s) for
protein amyloidosis in a host with reduced genome and
proteome.