FEB 13, 2016 8:19 AM PST

Bacteria's Killer Trait Becomes New Drug Delivery System

WRITTEN BY: Xuan Pham
R bodies in different states

Imagine a nanoscale needle that can pierce cells precisely and on command. Scientists from Harvard’s Wyss Institute for Biologically Inspired Engineering and Harvard Medical School (HMS) have developed just this, possibly revolutionizing the future of drug delivery.
 
Published in the American Chemical Society Synthetic Biology, the discovery adapts bacterial protein polymers known as “R bodies” into precise, retractable nanoneedles. Controlled by pH levels, the nanoneedles extend to puncture cell membranes to release encapsulated cargo. Once pH levels change, they quickly reverse to the coiled form, ready for action yet again.
 
"This is one of nature’s innovations, but the discovery here is our ability to translate this from nature into a system that we can now engineer and control," said Pamela Silver, senior author on the study and Wyss Core Faculty member.
 
In nature, R bodies are produced by the Paramecium endosymbionts as a form of deadly self-defense. R bodies exist as coiled proteinaceous ribbons at low pH. In response to being ingested by another bacterial strain, the “killer strain” uses the differences in pH levels to activate its killer trait – extension of the R bodies – to rupture the host cell’s membrane. Toxins are then released which kills the host paramecium.
 
Impressed by these biological javelins, the research team at Harvard adapted this defense mechanism into a new way to deliver drugs to targeted cells. They expressed and purified the R bodies from E. coli. They then fine-tuned the extension process by screening for mutants that have altered pH sensitivity. Ultimately, they derived at a system of synthetic pistons that respond to pH levels to puncture E. coli membranes, releasing encapsulated cargo.
 
"Our research establishes R bodies as biological machines that we can use to break through membranes,” said Jessica Polka, first author of the study. “These actuators don’t consume molecular fuel and are extremely robust; we believe they could one day be used to deliver material to mammalian cells."
 
The system has many advantages, including its tunable platform, which allows for controlled release of trapped content. The authors see this as a potential way to deliver toxins or other pharmaceutical payloads directly to targeted cells. For cancer, this system could more effectively kill tumor cells and reduce collateral damages to healthy cells.
 
Another property that makes this delivery system quite unique is its reversibility. Because the extension and retraction actions are purely mechanical, they can be controlled with great precision and can be re-used over and over again. This is highly beneficial considering the many compartments that are contained in eukaryotic cells.
 
The sky seems to be the limit for these new biological actuators. “By decorating these polymers with different kinds of metals or other materials with properties of interest, we could potentially develop a range of actuator-like, nanoscale structures," said Silver.
 
"There are so many amazing mechanisms engineered by Nature, and this is a great example of how we can mine living systems for unique biological elements and adapt them to develop programmable technologies for high value applications using synthetic biology," said Donald Ingber, Wyss Institute Founding Director.
 

Additional source: Wyss Institute
About the Author
  • I am a human geneticist, passionate about telling stories to make science more engaging and approachable. Find more of my writing at the Hopkins BioMedical Odyssey blog and at TheGeneTwist.com.
You May Also Like
AUG 23, 2019
Clinical & Molecular DX
AUG 23, 2019
Are Anti-Ebola Drugs Effective?
A deadly Ebola Virus Disease (EVD) caused by the Ebola virus triggers hemorrhagic fever in humans and some monkeys. The disease is highly infectious and is...
OCT 07, 2019
Genetics & Genomics
OCT 07, 2019
Risk Factors for Gout Revealed by Genome-Wide Association Study
Gout is a common type of arthritis, and causes severe and sudden pain, redness and swelling in the joints....
NOV 05, 2019
Clinical & Molecular DX
NOV 05, 2019
Meningitis and Encephalitis: Testing & Diagnosis Strategies for Effective Treatment
Meningitis is an inflammation of the membranes surrounding the brain (meninges) and spinal cord. Encephalitis, on the other hand, refers to inflammation of...
NOV 26, 2019
Immunology
NOV 26, 2019
The Immune System's Hand in Toxic Shock
While rare, toxic shock is a dangerous condition that acts fast and can be fatal. A new study identified a new target for treating toxic shock, a component...
JAN 07, 2020
Clinical & Molecular DX
JAN 07, 2020
Kiss and tell: new test for kissing bug disease
Here’s one Latin lover that you do not want to get kissed by: triatomines, or “kissing bugs”. Known locally as pitos or chipos, these ins...
JAN 22, 2020
Clinical & Molecular DX
JAN 22, 2020
Biosignatures detect TB infections months before symptoms appear
What if there was a test that could detect tuberculosis six months before symptoms appear? Researchers at the University of College London think a predicti...
Loading Comments...