The study shows how pathogenic bacteria can adapt to different conditions of the digestive system
Basic, acidic, basic again: For pathogenic bacteria like salmonella, the human digestive system is a sea change. So how might bacteria react to these changes? Now a team of researchers from the Max Planck Institute for Terrestrial Microbiology in Marburg led by Andreas Diebold has now provided a possible explanation: Pathogenic bacteria could alter components of the syringe device in flight – such as changing tires in a moving car – to enable a rapid response.
Some of the most well-known human pathogens – from the plague bacteria Yersinia pestis to the diarrheal pathogen Salmonella – use a small needle under the skin to inject disease-causing proteins into their host’s cells, thereby manipulating them. This needle is part of what is called the Type III Secretion System (T3SS), without which most of these pathogens cannot replicate in the body.
It is only recently that it was discovered that large parts of T3SS are not strongly attached to the main part of the system, but are constantly exchanging during the job. However, the significance of this phenomenon remained unclear. Researchers in Andreas Diebold’s laboratory at the Max Planck Institute for Terrestrial Microbiology discovered that this dynamic behavior allows bacteria to quickly adapt the structure and function of the injection device to external conditions.
Digestive system: a marine alteration of bacteria
Human digestion begins with a neutral to slightly alkaline environment in the mouth and esophagus, where the addition of gastric acids suddenly changes to severely acidic in the stomach – an environment in which many pathogens do not survive. The actual target of Yersinia enterocolitica, the disease-causing bacteria examined in the study, is the gut. Here, the conditions of neutral pH are restored.
But how can bacteria adapt so quickly to changing conditions, and how is this being controlled? PhD student Stefan Weimy, first author of the study, was able to demonstrate that a protein in the bacterial membrane acts as a pH-value sensor. In collaboration with the Ulrike Endesfelder laboratory at the Max Planck Institute, it was found that this protein becomes more mobile at a low pH (= acidic) and thus transmits the signal to T3SS components within bacteria.
Flexibility prevents misalignment
In an acidic environment such as the stomach, the moving components do not bind to the rest of the device (including the needle itself), so the injection system remains inactive. Once the bacteria enter a pH-neutral environment – as they are found in the gut – dynamic proteins aggregate, so that T3SS can quickly become active at these sites – potentially causing distress for the affected person.
Researchers speculate that the newly discovered effect may allow the bacteria to prevent “disruption” of the energy-consuming secretion system in the wrong environment, which could trigger the host’s immune response. On the one hand, the mobility and chassis dynamics allow for rapid reassembly and activation of the system under the right conditions.
Protein transport and exchange is increasingly being discovered in complexes and nanoparticles in all areas of life; However, the utility of these dynamics is often poorly understood. The new results from Marburg show how protein exchange allows to respond flexibly to external conditions – a huge advantage, not just for bacteria.
Wemi, S. Palinovic, A. Jekyll, H. Selinger, L. Lampaki, Dr. Weisman, E. Meuskens, I am. Linked.; Drescher, K. Endsfelder, U. Diebold, A.
Dynamic repositioning of the components of the type III cytosol secretion system prevents premature protein secretion at a low external pH
Nature Communications 12, 1625 (2021)