I just finished reading a paper in the penultimate issue of Cell regarding the structure of the complex formed by the interaction of the Listeria surface protein InIB and Met, the human receptor tyrosine kinase often implicated in cancers, especially lung cancer. While I neither care all that much about nor understand too many of the details of the structure of this complex, it raised an interesting question:

Could a mutant InIB be used probiotically as a lung cancer therapeutic? Because Listeria is dependent on this interaction for entry into cells (Listeria is an obligate intracellular bacterium and travels from cell to cell by rocketing itself through the cell membranes of the former and future host cells), and because InIB interaction with Met results in Met activation, Listeria expressing a functionally-mutated form of InIB would theoretically have limited virulence and would block Met from binding its ligand, HGF, and prevent its activation, which is often the case in cancer. Alternatively, purified mutant InIB could be isolated from modified Listeria and used as a Met inhibitor in the complete absence of potential for virulence. Furthermore, theoretically, this mutant bacterium could be used probiotically in large quantities to overcome active Listeria infections, or to at least limit the entry of those Listeria that have somehow escaped from cells, by reducing the relative local concentration of the wild-type, virulent form of InIB.

Please excuse the entire previous paragraph. I’m clearly thinking out loud, but they nonetheless remain interesting research questions. Does anyone know of studies that explore any of these questions? A quick search of PubMed reveals nothing for me—not even whether Listeria infections can increase the risk of cancer or whether probiotic strategis have ever been investigated as viable cancer therapeutics. This is, however, the only oncogene I know of that is also a target of a microbe, although I am almost certain other double targets exist.