Infectious prions cause diverse clinical signs and form an extraordinary range of structures, from amorphous aggregates to fibrils. How the conformation of a prion dictates the disease phenotype remains unclear. Mice expressing GPI-anchorless or GPI-anchored prion protein exposed to the same infectious prion develop fibrillar or nonfibrillar aggregates, respectively, and show a striking divergence in the disease pathogenesis. To better understand how a prion's physical properties govern the pathogenesis, infectious anchorless prions were passaged in mice expressing anchorless prion protein and the resulting prions were biochemically characterized. Serial passage of anchorless prions led to a significant decrease in the incubation period to terminal disease and altered the biochemical properties, consistent with a transmission barrier effect. After an intraperitoneal exposure, anchorless prions were only weakly neuroinvasive, as prion plaques rarely occurred in the brain yet were abundant in extracerebral sites such as heart and adipose tissue. Anchorless prions consistently showed very high stability in chaotropes or when heated in SDS, and were highly resistant to enzyme digestion. Consistent with the results in mice, anchorless prions from a human patient were also highly stable in chaotropes. These findings reveal that anchorless prions consist of fibrillar and highly stable conformers. The additional finding from our group and others that both anchorless and anchored prion fibrils are poorly neuroinvasive strengthens the hypothesis that a fibrillar prion structure impedes efficient CNS invasion.
Methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus pseudintermedius (MRSP) have been recognized as significant pathogens in veterinary medicine. There have been documented cases of MRSA infection and colonization in veterinary critical care units, in veterinary personnel, and in equine and feline patients. To date, there have been no studies examining the prevalence of MRSA or MRSP colonization of cats and dogs in animal shelters in the United States. The purpose of the current study was to determine the prevalence of MRSA and MRSP in cats and dogs in a northern Colorado animal shelter. Samples were collected from 200 cats and 200 dogs in an open admission shelter. Each species was divided into 2 smaller groups: 100 dogs or cats housed in the stray ward and 100 dogs or cats housed in the adoption area. Samples were evaluated for the prevalence of MRSA or MRSP, which was verified through aerobic culture and Kirby–Bauer agar disc diffusion to confirm antimicrobial sensitivity. Results revealed MRSA in 0.5% of cat samples, MRSA in 0.5% of dog samples, and MRSP in 3% of dog samples. These results are consistent with previously published prevalence rates for these 2 organisms in non-shelter populations of dogs and cats, indicating that cats and dogs from this Colorado shelter do not appear to pose any greater risk to the public than do cats and dogs in the general pet population.
Prions are the only protein aggregates that naturally transmit as infectious agents, and recently human to human transmission has occurred through transfusion of prion‐contaminated blood. Most cases of natural transmission start with a peripheral exposure followed by prion spread to the CNS. Yet certain prions do not invade the CNS, despite prion accumulation in non‐neural organs, such as spleen or heart. Intriguingly, all of these poorly neuroinvasive prions form fibrils, which are uncommon structures in prion disease. We are investigating the molecular basis for the remarkable differences between the spread of nonfibrillar and fibrillar prions to the brain using in vivo models. We have found that the fibrillar prions were more resistant to enzyme digestion and were extraordinarily stable when exposed to protein denaturing conditions, in mice and in humans. Taken together, these results provide evidence for a striking separation in the biochemical of fibrillar and nonfibrillar prions that underlie their differences in neuroinvasion. Grant Funding Source: NIH NS069566 and NS076896
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