Probing Acanthamoeba virulence using a multi-omics approach

Free-living amoebae of the genus Acanthamoeba are highly abundant in the environment. However, accidental contact with human tissue can render these protists pathogenic, capable of causing severe diseases in humans. One common condition involves the eye where the amoebae cause a painful infection of the cornea known as Acanthamoeba keratitis (AK), most prevalent in contact lens wearers. The amoebae contaminate contact lens storage cases where they grow to high densities, and upon contact with the eye, they adhere to the cornea and progress to deeper layers. An important precondition for the infection is considered to be the cell-to-cell contact of the amoebae with the cornea cells, which activates the pathogenic cascade. However, despite advancements in recent years, our understanding of this pathogenic cascade still remains unclear. It was not until 2013 that the first genome of Acanthamoeba was published. The advent of modern omics technologies now allow for very detailed analyses of the pathomechanisms of microorganisms. In this project, we apply an integrative omics approach to investigate the contact process of Acanthamoeba to human cells in the context of AK. Our experiments are based on our long-year experience with Acanthamoeba co-culture systems and involve modern proteomics methods coupled with transcriptome sequencing. We focus on the molecules released by Acanthamoeba before, during and after contacting with cornea cells and on subsequent gene expression changes in the amoebae. The current state of knowledge indicates that a wide array of molecules, of which only very few have been identified to date, is dynamically expressed by Acanthamoeba throughout the contact process. The data generated in this project will provide novel insights into the pathogenic cascade of Acanthamoeba and thus expand the current understanding of AK pathogenesis, potentially also paving the way for novel intervention strategies.