New Research Identify Pathways for Potential Treatment for Lethal Bacteria

Human intestine with intestinal bacteria. Kateryna Kon/Shutterstock

New research conducted by the Australian National University has identified pathways for lethal Clostridium spp. bacteria, potentially leading to more effective treatment options for the future.

“Our research shows there might be new therapies we could develop, such as using certain drugs to neutralise the toxin [released by the bacteria],” said the lead researcher, Prof. Si Ming Man, on May 21.

Man and his team’s research focused on the family of Clostridium bacteria that causes things like gas gangrene, sepsis and tetanus, all incredibly dangerous symptoms of an infection.

Gas gangrene and sepsis are life-threatening conditions; gas gangrene is a rare condition commonly caused by Clostridium infections; the bacteria creates air bubbles and toxins at the infection sites, killing the deep tissues.

Sepsis occurs when infections gets out of control when the bacteria enter the bloodstream, infecting many areas and causing extensive inflammation across many areas of the body.

One species the team looked into was the Clostridium septicum, an incredibly lethal bacteria that “kills four out of five people who get it within two days.”

The team observed that the bacteria could rapidly kill cells by releasing an a-toxin that acts “like a hammer” by punching holes in the cell’s surface.

The immune cells then detect the bacterial toxins and cellular damage, triggering them to activate an inflammatory pathway which can often cause more harm than good.

“The intention of the immune system is good—it’s trying to fight against the bacteria—but the infected cells also explode and die,” Prof. Man said.

The pathway activates inflammatory proteins called inflammasomes that kill the infected cells by punching holes in the infected cells, causing further cellular damage.

This induces immune cells to detect even more cellular damage and will activate even more inflammatory proteins and pathways, causing more tissue death and damage.

“When the bacteria spread and you have lots of dying cells all over the body, that’s when it can lead to sepsis and shock. That is why patients die very rapidly.”

While there are currently extremely limited treatment options, the researchers hoped that this study could provide further insight into the bacteria, leading to better outcomes for patients.

By experimenting with mice models and human immune cells, the team found the specific protein pathway the alpha-toxins target.

The toxins interact with immune cells and activate an immune protein called the NLPR3 inflammatory protein that induces further inflammation and damage across the body.

Subsequent tests confirmed that the protein could be stopped by the MCC950 molecule, a pre-existing protein in the body that specifically targets the NLPR3. The researchers also observed that an anti-toxin could also halt the propagation of the inflammatory response by blocking the Clostridium toxin, reducing its interaction with the immune system.

“There are drugs in the clinical trial stage right now that could block a key immune receptor that recognises the toxin, blocking our own immune system from responding to this toxin too violently,” Man said.

“Together, this could be a life-saving therapy.”