By transforming pathogenic bacterial toxins into analgesics, Harvard scientists open the door to new treatments

▎Editor of WuXi AppTec's content team Speaking of anthrax, many people know that it is an infectious disease caused by Bacillus anthracis
.

Human inhalation of Bacillus anthracis may cause severe lung infections.
Contact with Bacillus anthracis on the skin of humans and domestic animals may cause ulcers and necrosis, forming a scorched scab
.

Because of these pathogenic abilities, Bacillus anthracis has even been used as a biological weapon by terrorists, which is notorious
.

However, this terrible microorganism can exert unexpected benefits in the hands of some scientists
.

A few days ago, a research team led by Professor Isaac Chiu of Harvard Medical School transformed the toxin of Bacillus anthracis into a new analgesic therapy
.

Experimental results in mice show that the use of Bacillus anthracis toxin can not only eliminate various forms of pain, but also specifically target the neurons that mediate pain.
Therefore, this new analgesic method is expected to avoid affecting other parts of the body and reduce analgesics.
Common addictive effects
.

▲This study was published in the journal Nature Neuroscience under Nature.
This finding is quite surprising, because over the years, Professor Chiu’s team’s research on pathogenic microorganisms found that invading bacteria interact with the nervous system and often Produce and amplify pain, but few bacteria can alleviate or even eliminate pain
.

But they found that sensory neurons located in the dorsal root ganglion of the spinal cord, when in contact with specific proteins in the anthrax toxin, change the signal transduction in the cells, affecting them to transmit pain signals to the spinal cord
.

In the words of the researcher, the pain signal was "silent"
.

Specifically, the toxin produced by Bacillus anthracis contains protective antigen (PA), edema factor (EF) and lethal factor (LF)
.

When PA binds to the receptors of sensory neurons, a hole is formed for EF and LF to enter the nerve cells
.

A series of experiments have shown that not only the human nerve cells growing in the petri dish will be affected by the anthrax toxin, but also living animals will change the signal transmission of painful neurons due to the anthrax toxin
.

When the researchers injected the toxin into the end of the spinal cord of mice, it produced an effective analgesic effect, so that the mice could not perceive the pain caused by burning and mechanical stimulation
.

In addition, injecting mice with anthrax toxin can also relieve the other two kinds of pain: pain caused by inflammation and pain caused by nerve cell damage
.

Trauma, viral infections (such as shingles), complications of cancer treatment, etc.
, are common causes of these two types of pain
.

While the pain was reduced, the researchers observed the processed nerve cells and found that they were still physiologically intact.
This shows that the pain relief effect comes from changes in internal signals, not because the "hardware" that transmits the signals is destroyed
.

Image source: 123RF It is worth mentioning that because receptors that bind to anthrax toxin are only expressed on such pain-sensing nerve fibers, and other nerve cells have no related receptors, the effect of anthrax toxin can be accurately blocked in a small range.
The pain will be severed without extensively affecting the whole body
.

In fact, the researchers observed that after the experimental mice were treated with anthrax toxin for pain relief, their heart rate, body temperature, and exercise coordination were normal
.

Next, the researchers also extracted a part of the anthrax toxin to design a carrier that was used to bind other drug molecules and bring them together into the pain nerve cells
.

In this study, they tried to inject a toxin from another deadly bacteria, botulinum toxin, into the nerve cells
.

Botulinum toxin is also a toxin that can block nerve signals and is used by scientists to treat muscle cramps and pain
.

Experiments show that this new delivery method can also be used to relieve pain in mice
.

▲Professor Isaac Chiu’s research team is committed to understanding how microbes affect pain (picture source: Harvard Medical School official website) "This molecular platform uses bacterial toxins to deliver drugs to specific neurons and regulate their functions, which represents a targeted pain nerve It’s a new way of metamorphosis
.

" Professor Isaac Chiu, the corresponding author of this study, pointed out, "We use part of the anthrax toxin to be fused with the protein cargo we hope to deliver.
In the future, people can also let it deliver a variety of different proteins.
To provide targeted treatment
.

" However, the researchers also reminded that this method is still experimental.
It must be tested and optimized in more animal studies before being applied to humans, and the safety of toxin treatment must be carefully monitored.
In particular, the relationship between infection with Bacillus anthracis and the integrity of the blood-brain barrier must be considered
.

Although there is still a lot of work to be done to transform anthrax toxin into a good analgesic, this research also points out an important direction for finding analgesics, that is, there are many treasures in the natural world and the diverse microbial world.
Dig
.

References: [1] Yang, NJ, Isensee, J.
, Neel, DV et al.
Anthrax toxins regulate pain signaling and can deliver molecular cargoes into ANTXR2+ DRG sensory neurons.
Nat Neurosci (2021).
https://doi.
org /10.
1038/s41593-021-00973-8[2] Can a dangerous microbe offer a new way to silence pain? Retrieved Dec.
20, 2021 from https://