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Searched keyword : Zebrafish

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Identification of genes involved in the attenuation of virulence of rough M. abscessus Tn5 mutants in zebrafish

Mycobacterium abscessus is the fast growing mycobacterial species the most frequently associated with lung infection, characterized by severe and very inflammatory cases, after a slow and chronic infectious process. The Cystic Fibrosis patients are particularly susceptible to this bacteria. M. abscessus can exist in a smooth (S) or rough (R) shape depending respectively on the presence or absence of glycopeptidolipids (GPL) associated with the wall of the bacillus. These GPL are involved in motility and biofilm formation, two important features of bacterial colonization. A correlation between the morphotype R, capable of producing morphological structures called "cording" visible in microscopy, and virulence was established. Natural switching from a phenotype S to R allow the transition from a colonizing status to an invasive and pathogenic form. Our project is focusing on deciphering specific mechanisms and analysis of benefits from this transition S/R in vivo. On the basis of transcriptomic data and RNA-Seq previously obtained and/or by screening a transpositional library of colonies deficient in the cording formation, several genes were selected and their corresponding mutants were generated. Since are analyzed : i) the (glyco)lipid composition of their wall; ii) their respective virulence in zebrafish and mouse models and iii) the involvement/recruitment of macrophages and neutrophils and their role in inflammation in response to infection. Our aims are to identify and describe new virulence determinants specific to the establishment of chronic stages of M. abscessus and identification of molecular locks of the S/R switch to understand how an environmental mycobacterium evolves into a pathogen in the host.

Project status : Closed