Genetic Evidence of Protein Transfer during Bacterial Conjugation

DNA can be transferred from eubacteria to at least plants, fungi, and all other eubacteria by related, plasmid-mediated conjugation. Little is known about the biochemistry of intraspecies or interspecies DNA transfer. Even less is known about what other molecules may accompany the DNA, or the direct or inheritable effects on recipients of these escort molecules. This report describes a genetic assay for detecting protein transfer during conjugation. The assay monitored phage lambda released from lysogenic recipients as a result of the concomitant delivery of the Escherichia coli RecA protein and plasmid DNA. The heretofore unexpected transfer of a donor chromosome-encoded protein initiates a heritable change in the recipient without altering its genetic make-up. The mechanism of transfer could be independent of transferred DNA.     

Microbial specialization by prions

ABSTRACT

Microbial prions facilitate a variety of phenotypic switches. Recently-developed tools that can directly interrogate, in the living cell, the aggregation state of a protein have enabled a wider range of experiments for prion-mediated behaviors. With such tools, the roles of the yeast prion [SWI⁺] in migration and mating were studied. Although [SWI⁺] cells were consistently less fit than their [swi^?] counterparts under traditional laboratory conditions, in these new phenotypic paradigms [SWI⁺] cells demonstrated a distinct advantage. [SWI⁺] cells dispersed over a larger area under conditions resembling rainfall and outcrossed more frequently. We postulate that many behaviors in microorganisms may be modulated by stochastic prion switching. In diverse and changing natural environments, prion switching at low frequency may promote greater fitness of the population by specializing a small number of individuals with altered responses to their environments.     

Deer Carcass Decomposition and Potential Scavenger Exposure to Chronic Wasting Disease

ABSTRACT Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy afflicting the Cervidae family in North America, causing neurodegeneration and ultimately death. Although there are no reports of natural cross-species transmission of CWD to noncervids, infected deer carcasses pose a potential risk of CWD exposure for other animals. We placed 40 disease-free white-tailed deer (Odocoileus virginianus) carcasses and 10 gut piles in the CWD-affected area of Wisconsin (USA) from September to April in 2003 through 2005. We used photos from remotely operated cameras to characterize scavenger visitation and relative activity. To evaluate factors driving the rate of carcass removal (decomposition), we used Kaplan-Meier survival analysis and a generalized linear mixed model. We recorded 14 species of scavenging mammals (6 visiting species) and 14 species of scavenging birds (8 visiting species). Prominent scavengers included American crows (Corvus brachyrhynchos), raccoons (Procyon lotor), and Virginia opossums (Didelphis virginiana). We found no evidence that deer consumed conspecific remains, although they visited gut piles more often than carcasses relative to temporal availability in the environment. Domestic dogs, cats, and cows either scavenged or visited carcass sites, which could lead to human exposure to CWD. Deer carcasses persisted for 18 days to 101 days depending on the season and year, whereas gut piles lasted for 3 days. Habitat did not influence carcass decomposition, but mammalian and avian scavenger activity and higher temperatures were positively associated with faster removal. Infected deer carcasses or gut piles can serve as potential sources of CWD prions to a variety of scavengers. In areas where surveillance for CWD exposure is practical, management agencies should consider strategies for testing primary scavengers of deer carcass material.     

The end of the road

After some 60 years in research, a few months before my final retirement (there were a few temporary ones), the time has come to reminisce.     

Structure and function of the molecular chaperone Hsp104 from yeast

The molecular chaperone Hsp104 plays a central role in the clearance of aggregates after heat shock and the propagation of yeast prions. Hsp104's disaggregation activity and prion propagation have been linked to its ability to resolubilize or remodel protein aggregates. However, Hsp104 has also the capacity to catalyze protein aggregation of some substrates at specific conditions. Hence, it is a molecular chaperone with two opposing activities with respect to protein aggregation. In yeast models of Huntington's disease, Hsp104 is required for the aggregation and toxicity of polyglutamine (polyQ), but the expression of Hsp104 in cellular and animal models of Huntington's and Parkinson's disease protects against polyQ and α‐synuclein toxicity. Therefore, elucidating the molecular determinants and mechanisms underlying the ability of Hsp104 to switch between these two activities is of critical importance for understanding its function and could provide insight into novel strategies aimed at preventing or reversing the formation of toxic protein aggregation in systemic and neurodegenerative protein misfolding diseases. Here, we present an overview of the current molecular models and hypotheses that have been proposed to explain the role of Hsp104 in modulating protein aggregation and prion propagation. The experimental approaches and the evidences presented so far in relation to these models are examined. Our primary objective is to offer a critical review that will inspire the use of novel techniques and the design of new experiments to proceed towards a qualitative and quantitative understanding of the molecular mechanisms underlying the multifunctional properties of Hsp104 in vivo. © 2009 Wiley Periodicals, Inc. Biopolymers 93:252–276, 2010. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com     

A Non-amyloid Prion Particle that Activates a Heritable Gene Expression Program

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Prions,prionoids and pathogenic proteins in Alzheimer disease

Like patients with prion disease, Alzheimer patients suffer from a fatal, progressive form of dementia. There is growing evidence that amyloid-β (Aβ) aggregates may be transmissible similar to prions, at least under extreme experimental conditions. However, unlike mice infected with prion protein (PrP) prions, those inoculated with Aβ do not die. The transmission of Aβ and PrP thus differs conspicuously in the neurological effects they induce in their hosts, the difference being no less than a matter of life and death. Far from being a mere academic nuance, this distinction between Aβ and PrP begs the crucial questions of what, exactly, controls prion toxicity and how prion toxicity relates to prion infectivity.