Nowadays, people just take it for granted that ulcers and a variety of other gastric problems can be caused by bacteria. But it wasn't so long ago that mainstream science completely disdained the idea. Ah, it was all about the arrogance of how our bodies (specifically our stomachs) could somehow stop the microbes in their tracks.
In 1893, Guilio Bizzozero published the observation that there were spiral-shaped bacteria in the dog gut. This was confirmed by another scientist, Hugo Salomon, three years later. In the early twentieth century, W. Krienitz saw these spiral-shaped bacteria in the guts of patients who had stomach cancers. However, the medical and scientific establishment didn't pay much attention to these findings until the early 1980's. Robin Warren and Barry Marshall noticed the presence of Helicobacter pylori in inflammed areas of stomach biopsies. Frustrated that other specialists in the field didn't believe their observations, Marshall drank a broth of H. pylori* to prove his point.
But this doesn't mean that we're all passive hosts subject to the whims of our bacterial overlords. Bacteria in our gut can either be commensal or pathogenic and the host needs a way to distinguish between the two before the badly behaved bacteria wreak too much havoc. In the innate immune system, cells can sense bacteria through pattern-recognition receptors or PRRs. For macrophages, a type of mobile immune cell not unlike a cop in a patrol car, the PRRs are expressed on the surface. So whenever the PRRs come in contact with key bacterial motifs, the macrophage gets activated. Other types of cells, such as the epithelial cells in our gastrointestinal tract, get to see bacteria all the time. One would expect that these cells also express PRRs on the surface in order to detect bacteria. But this isn't the case! The PRRs in these cells are expressed internally instead.
If these receptors are expressed inside the cell, how on earth are they going to detect the bacteria outside? Here's the rub--they can detect bacteria from the inside because pathogenic bacteria are behaving badly. Intercellular pathogens think it's a great idea to get into the cell and make a little home for themselves. Once they get inside the cell, that's when they're caught. But what about the extracellular pathogens? That's where Viala et al. come in.
These researchers were working on Helicobacter pylori and the problem of how epithelial cells could sense the bacterium. H. pylori is an extracellular pathogen so one could ask, do the epithelial cells have some sort of sensor on their surface that helps detect the bacteria? In mice without Nod1, a type of PRR, H. pylori infection was more likely. But Nod1 is found inside epithelial cells, not outside. Viala et al. discovered that Nod1 was sensing the bacteria because H. pylori was injecting virulence factors into the cell by a type IV secretion apparatus** which acts like a syringe.
So a pathogen's bad behavior--whether it invades a cell or remains outside--is its undoing. Because many noninvasive pathogenic bacteria do secrete virulence factors into host cells while commensal bacteria don't, this actually turns out to be a great way for the host to distinguish between the good guys and the bad guys without triggering too many false alarms.
*This kind of thing seems amusing in hindsight, but please don't try this at home. Or at lab for that matter. Just take this anecdote as a reminder that we should try to be clever enough to devise experiments to prove a point without endangering ourselves.
**For the curious or for those who just need your memory refreshed, a secretion apparatus is basically a machine constructed of proteins which bridge the gap between the bacterial membranes and the host membrane to transport bacterial products into the host cell. The type IV secretion apparatus is related to the conjugation machinery in which bacteria exchange genetic material.
