02:32pm Friday 20 October 2017

Bacterial Injection Needle in 3D

stahlberg_T3SS_structure_small
Structure of the Yersinia enterocolitica T3SS infection apparatus (Left: cryoelectron tomography; Right: modeled 3D structure). (Image: University of Basel)

Bacteria have sophisticated mechanisms to infect their host cells. Pathogens, such as Yersinia pestis, the causative agent of plague, or Yersinia enterocolitica, which is causing Gastroenteritis, dispose of a specific infection apparatus, the Type III Secretion System (T3SS). This system can be thought of as a needle at the nanoscale, through wich the bacteria inject a cocktail of proteins and toxins towards and into human host cells. As part of the SNF Sinergia project headed by Prof. Guy Cornelis, the team of Prof. Henning Stahlberg from the Biozentrum, University of Basel has now for the first time been able to image the 3D structure of the T3SS in the intact membranes of two bacteria.

Flexible Infection Apparatus

The T3SS is found only in gram-negative bacteria and consists of about 30 different proteins. They form a needle-like structure whose base is anchored in the inner and outer membranes of the bacteria. The team of Stahlberg showed that the length of the membrane-bound base of the infection apparatus varies with the distance between these two membranes. The basal body’s length not only varies significantly among bacteria, but its length also adapts to changing environmental conditions.

Using highly-specialized methods such as cryoelectron tomography, X-ray crystallography, and computer modeling, the team around Stahlberg has succeeded in shedding light onto as yet unknown structural details of the intact T3SS of Y. enterocolitica. Structural studies of the entire complex in situ, and high-resolution structures of several of its protein components showed that the system is designed by nature for flexibility. Several proteins of the basal body can contract or expand. “When we anchored these proteins in a synthetic membrane,” explains Stahlberg, “they were shorter by about one third as in intact bacteria. In contrast, with a saline solution that expands the membrane spacing in life bacteria, the needle base was even more stretched.”

Useful Adjustment Mechanism

The researchers believe that the flexibility of the infection apparatus conveys a protective function to the fragile multi-protein complexes. This may help the bacteria to adapt to changing environmental conditions, while maintaining their potential for infection.

Original Citation
Mikhail Kudryashev, Marco Stenta, Stefan Schmelz, Marlise Amstutz, Ulrich Wiesand, Daniel Castaño-Díez, Matteo Degiacomi, Stefan Münnich, Christopher Bleck, Julia Kowal, Andreas Diepold, Dirk Heinz, Matteo Dal Peraro, Guy Cornelis, and Henning Stahlberg (2013)
In situ structural analysis of the Yersinia enterocolitica injectisome
eLife; Published online July 30, 2013 | doi: 10.7554/eLife.00792

 

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