FtxA, the novel virulence factor of Filifactor alocis as a modulator of microbial ecology and the immune response

The Gram-positive anaerobic rod Filifactor alocis is an emerging oral pathogen associated with multiple oral infections. We discovered in  F. alocis a hitherto unknown RTX toxin, which we named FtxA. It is homologous to B. pertussis adenylate cyclase toxin (ACT) CyaA and to A. actinomycetemcomitans leukotoxin LtxA.

FtxA is the 1st ACT and the 2nd RTX identified among the oral microbiome.The mechanisms by which it may act as a virulence factor of F. alocis to regulate the oral microbial ecology and immune response is an uncharted territory and the project´s main aim.

In the first segment of the project, clinical isolates and genetically manupulated F. alocis strains will be used to decipher the fucntional roles of FtxA in F. alocis microbe-microbe ecological competition and host-microbe immuno-pathogenic interactions of F. alocis. This approach will employ biofilms, immune cells and organotypic tissue in vitro models and metaproteomics.

In the second segment, the virulence contribution of FtxA will be evaluated in a murine model of F. alocis infection, using single-cell proteomics.

Moreover, the expression levels of FtxA will be evaluated in a cohort of periodontitis patients, where the oral levels of F. alocis have already been defined before and after treatment.

By deciphering the fucntional properties of FtxA , the project will lay the foundation for novel prevention and therapeutic strategies against infections caused by F. alocis or other RTX-producing species.