Bacteria with vuvuzelas: Microbes use a channel protein as a syringe for toxins

Mar 21, 2013
The toxin complex consists of three protein components: TcA (yellow), TcB and TcC (orange). The complex docks at receptor molecules on the membrane of the host cell and is being absorbed by endocytosis (left). A change in the pH value alters the 3 dimensional structure: the central channel is pushed through the cell membrane like the needle of a syringe (centre). TcB and TcC are thus drawn into the cell nucleus, where TcC is unpacked and loses its original structure. Credit: MPI of Molecular Physiology/Raunser

The bacterium Photorhabdus luminescens is a constant companion of some roundworms. These worms assault insect larvae, thereby infecting them with the bacteria; the pathogens then attack the cells of their victims with a deadly cocktail of various toxins. Scientists at the Max Planck Institute of Molecular Physiology in Dortmund working together with colleagues from Freiburg University and Jacobs University Bremen, have discovered that the bacteria use an important toxin complex like a syringe. It makes its way into the host cells via constricted vesicles in the cell membranes, and modifies their structure from within. Part of the toxin complex then forces its way inside the cell through the vesicle membrane by means of a vuvuzela-like protein channel, and kills the cell.

Important toxins of Photorhabdus luminescens are counted among the ABC toxins, which consist of the three TcA, TcB and TcC. The toxin complex first docks at on the membrane of the and is sucked inside the cell in small membrane blisters called vesicles. The TcC components then make their way into the cell fluid and demolish the cell's protein skeleton. What has remained unclear to date, however, was how the protein managed to get through the vesicle membrane.

Molecular vuvuzela: The central channel of the TcA proteins (light green) is shaped like a vuvuzela horn, the South African musical instrument (dark green: outer shell, black: cell membrane of the host cell). Credit: MPI of Molecular Physiology/Raunser

Now, for the first time, scientists have been able to decode the structure of Photorhabdus luminescens' ABC toxins using cryoelectron microscopy and single particle analysis. This shows that the bacterium's TcA protein consists of five subunits that together form the shape of a bell. "Inside the bell, the subunits form a channel that has one wide and one narrow aperture, so that it looks like the notorious vuvuzela horn used by South African football fans", explains Stefan Raunser of the Max Planck Institute of .

As soon as the pH value of the environment rises or falls, for example when the fluid in the vesicles turns acid, the of the toxin opens, unblocking the central channel. "Now the channel is pushed through the cell membrane like the needle of a syringe", says Raunser. TcB and TcC are drawn into the area between the channel and the shell, where TcC is unpacked and loses its original structure. "It may be that a drop in electrical tension or some specific unpacking proteins such as TcB are necessary for TcC to exit the vesicle and enter the cell, where it can unleash its deadly effects."

The results show that the TcA of roundworm bacteria is similar in shape to the toxins of the plague pathogen and other bacteria. "This may mean that these findings will also reveal the workings of bacteria that induce disease in humans", says Raunser. The findings could also help in the development of pest-resistant crops.

In addition to the ABC toxins, plague pathogens have developed another transport system that also occurs in the pathogens of dysentery and typhus. Known as the type III secretion system, it also looks like a syringe. However, the body of the syringe is embedded in the bacterial membrane, with the needle pointing outwards. The bacteria use these nanosyringes to inject material directly into their host cells.

Explore further: The malaria pathogen's cellular skeleton under a super-microscope

More information: Gatsogiannis, C. et al. Photorhabdus luminescens toxins use a novel syringe-like injection mechanism for cell entry, Nature, March 20, 2013. DOI: 10.1038/nature11987

Related Stories

Decoding the molecular machine behind E. coli and cholera

Feb 09, 2012

Scientists from Queen Mary, University of London have discovered the workings behind some of the bacteria that kill hundreds of thousands every year, possibly paving the way for new antibiotics that could treat infections ...

Targeting toxin trafficking

Jul 21, 2011

Toxins produced by plants and bacteria pose a significant threat to humans, as emphasized by the recent effects of cucumber-borne Shiga toxin in Germany. Now, new research published on July 21st by the Cell Press journal ...

Recommended for you

For resetting circadian rhythms, neural cooperation is key

16 hours ago

Fruit flies are pretty predictable when it comes to scheduling their days, with peaks of activity at dawn and dusk and rest times in between. Now, researchers reporting in the Cell Press journal Cell Reports on April 17th h ...

Rapid and accurate mRNA detection in plant tissues

17 hours ago

Gene expression is the process whereby the genetic information of DNA is used to manufacture functional products, such as proteins, which have numerous different functions in living organisms. Messenger RNA (mRNA) serves ...

For cells, internal stress leads to unique shapes

Apr 16, 2014

From far away, the top of a leaf looks like one seamless surface; however, up close, that smooth exterior is actually made up of a patchwork of cells in a variety of shapes and sizes. Interested in how these ...

User comments : 0

More news stories

Scientists tether lionfish to Cayman reefs

Research done by U.S. scientists in the Cayman Islands suggests that native predators can be trained to gobble up invasive lionfish that colonize regional reefs and voraciously prey on juvenile marine creatures.

Deadly human pathogen Cryptococcus fully sequenced

Within each strand of DNA lies the blueprint for building an organism, along with the keys to its evolution and survival. These genetic instructions can give valuable insight into why pathogens like Cryptococcus ne ...

Biologists help solve fungi mysteries

( —A new genetic analysis revealing the previously unknown biodiversity and distribution of thousands of fungi in North America might also reveal a previously underappreciated contributor to climate ...

Leeches help save woman's ear after pit bull mauling

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

Venture investments jump to $9.5B in 1Q

Funding for U.S. startup companies soared 57 percent in the first quarter to a level not seen since 2001, as venture capitalists piled more money into an increasing number of deals, according to a report due out Friday.