SEP 27, 2016 10:44 AM PDT

Anthrax Toxin is Shuttled Across Membrane and Into Cells

WRITTEN BY: Carmen Leitch
2 4 338
Anthrax is commonly found in soil and can be ingested by animals. It is relatively rare for it to affect people but when it does, it can cost a variety of symptoms and it can be a deadly infection. A three dimensional map of anthrax toxin has now been created by researchers, and the structure may explain how deadly components infect cells and cause disease.
The crystal structures of the anthrax toxin LF and PA subunits are superimposed on the 3-D map of the prepore complex obtained by cryo-electron microscopy. The side view (left) and top-down view (right) show three LF molecules perched above the rim of the pore formed by seven PA subunits. / Credit: JGP Fabre et al

During infection by Bacillus anthracis, anthrax toxin is secreted. There are three parts of soluble proteins that compose the toxin. Similar enzymes make up two parts of it, enzymes called lethal factor (LF) and edema factor (EF); another protein called protective antigen (PA) is the third piece. They all bind together and are taken into cells by vesicles called endosomes. Seven or eight PA proteins subsequently form a channel in the membrane of the endosomes, which lets LF and EF move into the cytoplasm. There, the proteins are able to damage or even kill the cell.

That channel that forms in the endosomal membrane is critical; LF and EF unfold in the lumen of the endosome to be able to pass through the pore. They then are able to reform into their active structures once in the cytoplasm. If you would like to know more about the general pathogenesis of Bacillus anthracic, check out the video below.
 


The work was performed by a team of investigators led by Robert Liddington of the Sanford Burnham Prebys Medical Discovery Institute in La Jolla and by Isabelle Rouiller of McGill University in Montreal. It has been published in The Journal of General Physiology.

The team used cryo-electron microscopy to construct a 3D map of the so-called prepore complex that PA and LF form just prior to translocating. The map illustrated seven PA proteins encircling a narrow pore, complete with three LF molecules ready at the rim for translocation. In addition to binding to the PA subunits, the LF molecules also bound to its neighbor. The scientists have suggested that the interactions between LF particles can hold the deadly enzymes in place, preventing them from premature unfolding.

Additionally, as one LF molecule goes into the channel, its neighbor is destabilized such that it can follow behind, going into the pore immediately. That leaves space on the rim of the pore for additional molecules, forming a continuous chain of molecules streaming into the cytoplasm.

Electrophysiological measurements taken by the researchers of the prepore complex support the theory that molecules can be continuously translocated. "We have demonstrated that the anthrax pore can translocate full-length LF in a highly efficient, fast, and robust fashion," explained Rouiller. "The pore can effectively remain fully loaded for extended periods, acting as a conveyer belt while translocating a continuous 'daisy chain' of deadly LF molecules."
 


For a less technical look at how anthrax affects human health, what it can do to people, and how it is treated, check out the video above.

Sources: CDC, Science Daily via The Rockefeller University Press, The Journal of General Physiology
 
About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
MAY 07, 2018
Microbiology
MAY 07, 2018
West Nile Virus May Now Have a Treatment
West Nile Virus is a mosquito-borne disease with no effective treatments and no vaccine. That may be changing.
MAY 08, 2018
Genetics & Genomics
MAY 08, 2018
A Genetic Assessment of a Drug-resistant Pathogen
Drug resistance is a growing threat to public health and is responsible for the death of around 23,000 people every year in the US alone.
JUN 04, 2018
Microbiology
JUN 04, 2018
Neutralizing Infections with Nanotechnology
Clearing bacterial infections from the body can present challenges. Engineers are trying to use nanorobots for such situations.
JUN 30, 2018
Videos
JUN 30, 2018
First US Case of Bubonic Plague in 26 Years is Reported
It's not known exactly where the patient contracted the disease, but it was either Idaho or Oregon.
AUG 13, 2018
Microbiology
AUG 13, 2018
Insight Into the Origins of Junk DNA - From Koalas
The human genome isn't only genes. There's also long, repetitive sequences with an unknown function and origin.
AUG 14, 2018
Microbiology
AUG 14, 2018
Germs are Gaining Resistance to Hand Sanitizers
Alcohol-based hand sanitizers are not as effective as they once were.
Loading Comments...