Human pathogens prevent "misfiring" of their type III secretion system by sensing pH

Pathogenic bacteria such as Yersinia enterocolitica or the diarrhea pathogen Salmonella, have to pass the human digestive tract to then become active in the host's intestines. They use a tiny needle to inject the disease-causing toxins into their host's cells, which is part of the so-called type III secretion system (T3SS). It was only recently discovered that large parts of the T3SS are not firmly anchored to the main part of the system, but are constantly exchanging during function. However, the significance of this phenomenon remained unclear.
Our research collaboration led by Andreas Diepold at the Max Planck Institute for Terrestrial Microbiology now has revealed that this dynamic behavior allows the bacteria to quickly adapt the structure of their needle systems to external conditions: We were able to show that a T3SS protein in the cellular membrane functions as a pH sensor and, in an acidic environment like the stomach, becomes motile (as seen in the picture: the dark blue fraction of the motility distribution becomes prominent when the bacteria are exposed to acidic conditions.).
In this conformational state of the membrane-anchored needle complex, the mobile, cytosolic T3SS components (e.g. delivering the toxin molecules for their export to the needle) cannot bind and the injection system remains inactive. As soon as the bacteria enter a pH-neutral environment – e.g. when reaching the intestine – the membrane complex rebuilds and the T3SS system becomes active again.
This newly discovered mechanism may allow the bacteria to prevent an energy-consuming "misfiring" of the secretion system in the wrong environment ("wasting toxins" by secreting them while e.g. transiting through the host's stomach") and which may even activate the host's immune response. On the other hand, the fast remodeling of the structure allows the system to be rapidly reassembled and activated under appropriate conditions (in contrast to building the whole complex from scratch).

Our work is now published in Nature Communications.