No abstract

Prions are unconventional agents composed of misfolded prion protein that cause fatal neurodegenerative diseases in mammals. Prion strains induce specific neuropathological changes in selected brain areas. The mechanism of strain-specific cell tropism is unknown. We hypothesised that prion strains rely on different endocytic routes to invade and replicate within their target cells. Using prion permissive cells, we determined how impairment of endocytosis affects productive infection by prion strains 22L and RML. We demonstrate that early and late stages of prion infection are differentially sensitive to perturbation of clathrin- and caveolin-mediated endocytosis. Manipulation of canonical endocytic pathways only slightly influenced prion uptake. However, blocking the same routes had drastic strain-specific consequences on the establishment of infection. Our data argue that prion strains use different endocytic pathways for infection and suggest that cell type-dependent differences in prion uptake could contribute to host cell tropism.

C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis, a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs) and c-di-GMP-degrading enzyme phosphodiesterases (PDEs) in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera. Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium.

A study on the ecological distribution of alveolar Echinococcus was carried out in the Hulunbeier Pasture of Inner Mongolia, China during 1998 and 1999. Animals examined included wolves (Canis lupus), red foxes (Vulpes vulpes), sand foxes (Vulpes corsac), domestic dogs (Canis familiaris), Microtus brandti, Meriones unguiculatus, Citellus dauricus, Allactaga sibirica, Phodopus sungorus and Ochotona daurica. Three wolves were found to be infected with E. granulosus. Two sand foxes were infected with E. multilocularis. The majority of infections of alveolar echinococcus was found in M. brandti. Based on the structure of metacestodes found in the livers of naturally infected M. brandti, 3 main variants were observed. Type I had small alveolar cysts with thin cyst walls. Type II had a larger cyst with a thick cyst wall. Infection of laboratory mice with the gravid segments isolated from the naturally infected sand foxes led to the formation of mature Type I alveolar metacestodes in the lungs and Type II metacestodes in the livers of infected animals, respectively.