Few microbiologists are likely to forget the moment when the sheer scale and diversity of the microbial world became apparent to them. Similarly, it is a sobering thought that, in (or more accurately on) the human body, bacteria outnumber human cells by at least 10 to 1. Fortunately, most of these bacteria behave as good guests should, and they are content to remain on the other side of the physical barriers that separate us from the outside world. It is inevitable that at such a large gathering, some guests, the pathogens, will misbehave, and worse, start a fight. For many years it was thought that the battle between host and pathogen at the mucosal membranes was fought at arm's length. The bacteria lobbed toxins and other noxious agents at the host and the host returned the favor with antibodies. Bacteria that ventured too close were rapidly dispatched by the professional killing machines, the phagocytic cells. Some bacteria, such as Mycobacterium tuberculosis, however, proved inconveniently recalcitrant to intracellular killing and could become permanent guests within macrophages. Nonetheless, despite the appreciation that mitochondria originate from intracellular bacteria, the notion that mucosal pathogens could be intimately involved with nonprofessional phagocytes is relatively new.

We now know that a wide variety of organisms are capable of directing their own entry into epithelial cells and other host nonphagocytic cells. These bacteria engage in a remarkably sophisticated molecular dialogue with host cells in order to manipulate signal transduction pathways and effectuate bacterial entry.