Fighting bacteria and genetic disease with breast milk ‘bio-bullets’

Microscopic protein fragments found in breast milk could be used against antimicrobial resistance and genetic disorders

 
Rohanah Hussain, Senior Beamline Scientist, on Diamond's B23 beamline which was used in the research 
 
Scientists have used Diamond to create a bacteria-killing, drug-delivering capsule made from protein fragments found in breast milk. Their results are published in Chemical Science.
 
Breast milk provides a range of nutrients to support a growing infant, but it also contains a special protein called lactoferrin. This naturally-occurring anti-microbial protects babies from a range of infections, including bacteria, viruses and fungi.
 
It is just a tiny portion of lactoferrin that causes it to be so effective against infection. These minute fragments appear to cluster together before attacking bacterial cells. By all targeting the same point, the protein fragments can disrupt the outer wall of the bacteria, eventually killing it completely.
 
But now, a group from the National Physical Laboratory (NPL) and University College London (UCL) has re-engineered these naturally-occurring lactoferrin fragments to create a virus-like organism that detects and attacks bacterial cells with a bullet-like force.
 
The group engineered the fragments to self-assemble into a capsule structure – the same structure that viruses use to penetrate host cells. These capsules act like bullets, tearing through the outer membranes of bacterial cells, ultimately destroying them.
 
Using the cutting-edge facilities at the University of Bristol’s cryo-scanning electron microscope, matched with Diamond’s B21 and B23 beamlines, the group were able to explore this process in atomic detail. Hasan Alkasseem, a joint NPL/UCL EngD student who worked on the project, commented:
 
“To monitor the activity of the capsules in real time we developed a high-speed measurement platform using atomic force microscopy. The challenge was not just to see the capsules, but to follow their attack on bacterial membranes. The result was striking: the capsules acted as projectiles porating the membranes with bullet speed and efficiency."
 
Despite this ferocity towards bacteria, the capsules leave human cells unharmed. That’s because, whilst they are capable of entering human cells, they contain none of the damaging genetic material that viruses use to infect their host.

 

Viruses survive by invading host cells and then releasing genetic information inside. The virus hijacks the cell’s infrastructure so that it is forced to replicate this genetic information again and again: that’s how viruses are able to spread through the body.
 
Without this genetic information, the capsules pose no risk to human cells. But because of their virus-like structure, they do have the potential to release information into host cells if that’s what we wanted.
Whilst extremely harmful coming from a virus, the hijacking and replication process could prove highly useful if the capsules were to release genes that had a positive effect on the host.
 
Gene therapy is the practice of inserting new genes into the body that replace or shut off the body’s own defective genes. This approach is being studied as a tool to treat a range of genetic diseases including cystic fibrosis, cancer, sickle cell disease and some forms of muscular dystrophy.
 
His group’s success in creating an empty capsule assembled from protein fragments could be a significant step forward for gene therapy, as it presents a new way of transporting genes into the body’s cells.
 
The UCL and NPL group tested the ability of their capsules to transport genes in this way and found them to be successful. They inserted model genes designed to prevent a certain process taking place within human cells. When the capsules delivered these new genes, they found that the target process was indeed stopped.
 
This group’s discoveries have profound implications for efforts to tackle antimicrobial resistance and genetic disease. The work is still in its early stages, but if it continues it could prove a potent method for destroying bacteria and providing gene therapy – this would make it a ground-breaking finding for medical research.
 
Rohanah Hussain is Senior Beamline Scientist on B23, one of the beamlines used in the research. She observes: “The ability to scrutinise biological processes on the atomic scale is revolutionising our approach to health and medicine. As technology continues to develop, we’re likely to see more and more drugs emerging that are highly targeted at the molecular level. Ultimately, this revolutionary shift is only possible thanks to our growing knowledge of the biological world at its deepest and most intricate level.”
 
 
 The findings may provide new approaches for antimicrobial engineering and gene therapy