The prion protein-encoding gene (prnp) strongly influences the susceptibility of small ruminants to transmissible spongiform encephalopathies (TSEs). Hence, selective breeding programs have been implemented to increase sheep resistance to scrapie. For goats, epidemiological and experimental studies have provided some association between certain polymorphisms of the cellular prion protein (PrP C ) and resistance to TSEs. Among them, the Q/K polymorphism at PrP C codon 222 (Q/K 222 ) yielded the most promising results. In this work, we investigated the individual effects of the K 222 -PrP C variant on the resistance/susceptibility of goats to TSEs. For that purpose, we generated two transgenic mouse lines, expressing either the Q 222 (wild type) or K 222 variant of goat PrP C . Both mouse lines were challenged intracerebrally with a panel of TSE isolates. Transgenic mice expressing the wildtype (Q 222 ) allele were fully susceptible to infection with all tested isolates, whereas transgenic mice expressing similar levels of the K 222 allele were resistant to all goat scrapie and cattle BSE isolates but not to goat BSE isolates. Finally, heterozygous K/Q 222 mice displayed a reduced susceptibility to the tested panel of scrapie isolates. These results demonstrate a highly protective effect of the K 222 variant against a broad panel of different prion isolates and further reinforce the argument supporting the use of this variant in breeding programs to control TSEs in goat herds.
IMPORTANCEThe objective of this study was to determine the role of the K 222 variant of the prion protein (PrP) in the susceptibility/resistance of goats to transmissible spongiform encephalopathies (TSEs). Results showed that transgenic mice expressing the goat K 222 -PrP polymorphic variant are resistant to scrapie and bovine spongiform encephalopathy (BSE) agents. This protective effect was also observed in heterozygous Q/K 222 animals. Therefore, the single amino acid exchange from Q to K at codon 222 of the cellular prion protein provides resistance against TSEs. All the results presented here support the view that the K 222 polymorphic variant is a good candidate for selective breeding programs to control and eradicate scrapie in goat herds.
The insertion of an
implant in the body of a patient raises the risk of a posterior infection
and formation of a biofilm, which can have critical consequences on
the patient’s health and be associated with a high sanitary
cost. While antibacterial agents can be used to prevent the infection,
such a strategy is time-limited and causes bacteria resistance. As
an alternative to biochemical approaches, we propose here to use light-induced
local hyperthermia with plasmonic nanoparticles. This strategy is
implemented on surgical meshes, extensively used in the context of
hernia repairing, one of the most common general surgeries. Surgical
meshes were homogeneously coated with gold nanorods designed to efficiently
convert near-infrared light into heat. The modified mesh was exposed
to a biofilm of Staphylococcus aureus (S.
aureus) bacteria before being treated with a train of light
pulses. We systematically study how the illumination parameters, namely
fluence, peak intensity and pulse length, influence the elimination
of attached bacteria. Additionally, fluorescence confocal microscopy
provides us some insight on the mechanism involved in the degradation
of the biofilm. This proof-of-principle study opens a new set of opportunities
for the development of novel disinfection approaches combining light
and nanotechnology.
Early studies in transgenic mouse lines have shown that the coexpression of endogenous murine prion protein (PrPC) and transgenic PrPC from another species either inhibits or allows the propagation of prions, depending on the infecting prion strain and interacting protein species. The way whereby this phenomenon, so-called “interference,” is modulated remains to be determined. In this study, different transgenic mouse lines were crossbred to produce mice coexpressing bovine and porcine PrPC, bovine and murine PrPC, or murine and porcine PrPC. These animals and their respective hemizygous controls were inoculated with several prion strains from different sources (cattle, mice, and pigs) to examine the effects of the simultaneous presence of PrPC from two different species. Our results indicate interference with the infection process, manifested as extended survival times and reduced attack rates. The interference with the infectious process was reduced or absent when the potentiality interfering PrPC species was efficiently converted by the inoculated agent. However, the propagation of the endogenous murine PrPSc was favored, allowing us to speculate that host-specific factors may disturb the interference caused by the coexpression of an exogenous second PrPC.
IMPORTANCE Prion propagation can be interfered with by the expression of a second prion protein in the host. In the present study, we investigated prion propagation in a host expressing two different prion protein genes. Our findings indicate that the ability of the second prion protein to interfere with prion propagation is related to the transmissibility of the prion in the host expressing only the interfering prion protein. The interference detected occurs in a prion strain-dependent manner. Interestingly, a bias favoring the propagation of the murine PrP allele has been observed. These results open the door to future studies in order to determine the role of host factors other than the PrP amino acid sequence in the interference in prion propagation.
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