Functional amyloids as inhibitors of plasmid DNA replication.

DNA replication is tightly regulated to constrain the genetic material within strict spatiotemporal boundaries and copy numbers. Bacterial plasmids are autonomously replicating DNA molecules of much clinical, environmental and biotechnological interest. A mechanism used by plasmids to prevent over-replication is 'handcuffing', i.

Pre-amyloid oligomers of the proteotoxic RepA-WH1 prionoid assemble at the bacterial nucleoid.

Upon binding to short specific dsDNA sequences in vitro, the N-terminal WH1 domain of the plasmid DNA replication initiator RepA assembles as amyloid fibres. These are bundles of single or double twisted tubular filaments in which distorted RepA-WH1 monomers are the building blocks. When expressed in Escherichia coli, RepA-WH1 triggers the first synthetic amyloid proteinopathy in bacteria, recapitulating some of the features of mammalian prion diseases: it is vertically transmissible, albeit non-infectious, showing up in at least two phenotypically distinct and interconvertible strains.

Interferon-associated retinopathy in a patient with metastatic melanoma.

We present the unusual case of a 35 year-old woman with stage IV melanoma and widespread metastases, who was undergoing treatment with interferon alpha-2b and who presented with interferon-associated retinopathy. The patient, who had been taking interferon treatment for three months, complained of a sudden loss of visual acuity in the left eye. An ocular examination revealed multiple cotton wool spots along the retina and macular involvement.

Direct assessment in bacteria of prionoid propagation and phenotype selection by Hsp70 chaperone.

Protein amyloid aggregates epigenetically determine either advantageous or proteinopathic phenotypes. Prions are infectious amyloidogenic proteins, whereas prionoids lack infectivity but spread from mother to daughter cells. While prion amyloidosis has been studied in yeast and mammalian cells models, the dynamics of transmission of an amyloid proteinopathy has not been addressed yet in bacteria.

RepA-WH1 prionoid: a synthetic amyloid proteinopathy in a minimalist host.

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.