Already in 1868, the German physicians W. Busch and F. Fehleisen identified the potential of bacteria to treat cancer patients. Since then, many different bacteria have been studied for their potential in oncotherapy and many bacteria have been shown to preferentially replicate within solid tumors. Coming from the field of microbiology we have learned to master a bacterial weapon, the “type three secretion system” (T3SS). This needle-like structure allows direct transport of proteins from the bacteria into eukaryotic cells and is used by many pathogenic bacteria. We adapted this nano-machinery to deliver functional human proteins of our choice.  Now, together with our collaborator from the field of oncology, Prof. G. Christofori, we aim to assess the potential of these engineered bacteria to kill tumor cells in a mouse model of cancer. In addition to the increased cytotoxicity of bacteria, we plan to make use of tumor microenvironment specific bacterial promoters. The tumor microenvironment has special features as hypoxia. Bacterial promoters that are induced by hypoxic conditions have been described. We will use such promoters to drive the transcription of essential genes, which we deleted on the bacterial chromosome. Resulting bacteria can only replicate within a tissue allowing expression of the essential gene, which will lead to an enhanced tropism of bacteria to the tumor tissue and reduced damage to non-related tissue.