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Projeto de investigação
Find targets for Clostridium difficile infection control.
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Autores
Publicações
Assembly of the Clostridioides difficile spore surface layers
Publication . Marini, Eleonora; Henriques, Adriano O.
"Clostridioides difficile is a strict, anaerobic, gram-positive spore-forming bacterium and the leading cause, worldwide, of hospital acquired antibiotic associated diarrhea. It causes a range of intestinal conditions whose symptoms include mild diarrhea but also more serious and potentially life-threatening conditions including pseudomembranous colitis, toxin megacolon, bowel perforation and sepsis. The C. difficile infection cycle begins with the ingestion of spores. Once ingested, spores can germinate in the small intestine in response to bile salts, leading to the formation of a population of cells able to produce the two main virulence factors, the cytotoxins TcdA and TcdB, and more spores. Shedding of the oxygen-resistant spores into the environment allows dissemination of the organism and the infection of new hosts. (...)"
Characterization of biofilm formation by Clostridioides difficile
Publication . Bonneville, Lourenço Maria Corrêa Monteiro Cayolla; Serrano, Mónica; Henriques, Adriano
Clostridioides difficile is an urgent threat level enteric pathogen, that can produce endospores, toxins and biofilms. This work focused on understanding the regulatory circuits controlling gene expression during biofilm formation in C. difficile. We characterized the Veg protein, a highly conserved protein among Gram-positive bacteria, and that in B. subtilis was shown to stimulate biofilm formation by inducing biofilm-specific gene expression. Veg, is a 10 kDa, Sm-like protein. Sm proteins form multimers that bind to RNA. We show that overproduction of Veg also stimulated biofilm formation in a C. difficile lab strain. In vitro the oligomeric state of Veg is pH-dependent and shifts the protein from monomer to dimer and higher order protein complexes. We have no evidence for binding to RNA but we show that Veg binds to DNA, specifically to a TA rich region in the cdeM promotor. cdeM is a late sporulation gene involved in assembly of the spore surface layers and whose expression is dependent on yabG, the gene adjacent to veg, coding for a cysteine protease. We propose a model of repression of cdeM by Veg, that could be lifted by proteolysis of Veg by YabG.
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Entidade financiadora
Fundação para a Ciência e a Tecnologia
Programa de financiamento
3599-PPCDT
Número da atribuição
PTDC/BIA-MIC/29293/2017