7 research outputs found
A Dominant-Negative Approach That Prevents Diphthamide Formation Confers Resistance to Pseudomonas Exotoxin A and Diphtheria Toxin
Diphtheria toxin (DT), Pseudomonas aeruginosa Exotoxin A (ETA) and cholix toxin from Vibrio cholerae share the same mechanism of toxicity; these enzymes ADP-rybosylate elongation factor-2 (EF-2) on a modified histidine residue called diphthamide, leading to a block in protein synthesis. Mutant Chinese hamster ovary cells that are defective in the formation of diphthamide have no distinct phenotype except their resistance to DT and ETA. These observations led us to predict that a strategy that prevents the formation of diphthamide to confer DT and ETA resistance is likely to be safe. It is well documented that Dph1 and Dph2 are involved in the first biochemical step of diphthamide formation and that these two proteins interact with each other. We hypothesized that we could block diphthamide formation with a dominant negative mutant of either Dph1 or Dph2. We report in this study the first cellular-targeted strategy that protects against DT and ETA toxicity. We have generated Dph2(C-), a dominant-negative mutant of Dph2, that could block very efficiently the formation of diphthamide. Cells expressing Dph2(C-) were 1000-fold more resistant to DT than parental cells, and a similar protection against Pseudomonas exotoxin A was also obtained. The targeting of a cellular component with this approach should have a reduced risk of generating resistance as it is commonly seen with antibiotic treatments
Cough symptoms in children aged 5-14 years in Sydney, Australia: non-specific cough or unrecognized pertussis?
Consumer Preferences for Baobab Products and Implication for Conservation and Improvement Policies of Forest Food Resources in Niger (West Africa)
Forests and global change: what can genetics contribute to the major forest management and policy challenges of the twenty-first century?
Difteria pelo Corynebacterium ulcerans: uma zoonose emergente no Brasil e no mundo
O artigo revisa a literatura sobre a emergĂȘncia de infecçÔes humanas causadas por Corynebacterium ulcerans em diversos paĂses, incluindo o Brasil. Foi realizada anĂĄlise de artigos publicados entre 1926 e 2011 nas bases Medline/PubMed e SciELO, bem como artigos e informes do MinistĂ©rio da SaĂșde. Apresenta-se um esquema de triagem, rĂĄpido, econĂŽmico e de fĂĄcil execução, capaz de permitir a realização do diagnĂłstico presuntivo de C. ulcerans e C. diphtheriae na maioria dos laboratĂłrios brasileiros pĂșblicos e privados. A circulação de C. ulcerans em vĂĄrios paĂses, aliada aos recentes casos de isolamento do patĂłgeno no Rio de Janeiro, Ă© um alerta a clĂnicos, veterinĂĄrios e microbiologistas sobre a ocorrĂȘncia de difteria zoonĂłtica e a circulação do C. ulcerans em regiĂ”es urbanas e rurais do territĂłrio nacional e/ou da AmĂ©rica Latina