As we know, the resistance
that bacteria have against our antibiotics is growing at an alarming rate. To
make it even worse, these microorganisms have the capacity to form biofilms,
where bacteria band together in groups and produce a sticky substance that protects
them from external threats like antibiotics.
Imagine them using biofilm much
in the same way as when we build houses to protect us from the rain and cold.
To wipe out such bacterial
infections, we have to find new tools to break into and destroy these biofilms.
And now we have. Using a clever combination of DNA and nanotechnology we have found
a way to conquer this «Chateau Bacteria».
Summary of the article
Bacterial biofilms can be broken into and destroyed by using nanoparticles that carry antibiotics and pierce into the biofilm structure. One example is to use drug-loaded DNA-based micelles, tiny molecular assemblies, to penetrate deep into the biofilm.
In the lab, these micelles broke into the biofilm in just two hours and killed the bacteria, without any signs of damage to skin cells.
This approach could be a new therapy against biofilms that are formed in wounds and unlock the full potential of using DNA against antimicrobial resistance.
This short version was made with AI/ChatUiT
The castle walls
These biofilms can be
formed on different surfaces, for example in medical instruments or in our own
bodies, such as the skin. This biofilm formation is particularly alarming as
these structures are highly tolerant to antibiotics, meaning that it is very
hard to penetrate that protective wall and kill the bacteria inside.
The formation of a biofilm
on the skin is particularly scary if the skin is damaged, for example if you
have an open wound. In those cases, biofilms are very difficult to remove, and
antibiotics penetrate the biofilm very poorly. This means that most bacteria
living inside the biofilm will survive.
After painting this
alarming picture, what are our options in the fight against the biofilm and the
bacteria? What kind of siege weapons do we have in our arsenal? Until now, not
Nanotechnology to the
making really, really, really small particles. They can be up to a million
times smaller than an ant. Nanoparticles can be made from many different
materials like polymers (molecules strung together), lipids (fat or oils) or non-organic
materials like silver or gold.
These particles are
incredibly versatile, and in modern medicine for example, they can be used in both
diagnostics, imaging, and drug delivery – transporting medicine to the right
spot in our body.
By changing the physical
and chemical properties of nanoparticles, we can give them the ability to carry
antibiotics that penetrate the walls of the biofilm house, and then release it
inside the «castle walls».
The new star of the drug delivery show
But recently, a new star joined
the show: good old DNA.
This ancient material is a
reliable ally because you can program it to be in whatever shape and size you like
without obvious toxicity. It has already been explored for use in cancer
therapy, but could this old friend of ours be used for something else too?
Many successful approaches by
other researchers have shown that nanoparticles were effective in delivering
antibiotics against biofilms. However, the problem with DNA is that it both dissolves
in water and has a negative electric charge. This is a problem when you are
trying to attack biofilms, so we thought:« is there a way to tweak some of
these properties in order for the DNA-nanoparticles to penetrate the biofilm?»
To make it short: Yes,
Cholesterol – the
We decided to modify a DNA
sequence by attaching a cholesterol molecule to it. Since cholesterol does not
dissolve in water, the fat molecules tend to group together the same way it
happens when we add oil in a pan of boiling water to cook pasta. The drops of
oil come together to create oil bubbles.
By combining DNA and
cholesterol, we were able to create tiny particles called micelles. The
cholesterol is inside the micelle, and the outer layer of the nanoparticle is
made up of DNA.
Our next question was,
could we use this for drug delivery? Yes again!
When we added Polymyxin B, a
last resort antibiotic used against the bacteria Pseudomonas aeruginosa, to the cholesterol-DNA, the whole particle structure
became more stable. This has not been reported before, and it gave us a better
understanding of how to combine antibiotics with modified DNA structures.
The next action hero
This finding was
interesting, but we wanted to take it to the next level and explore if it could
penetrate into the biofilm. That doesn’t happen easily, but to our enthusiasm,
these drug-loaded DNA-based micelles – the nanoparticles - penetrated deep into
the biofilm structure in just two hours!
The story got even better
by observing that the antibiotic kept its effectiveness, killing the bacteria
inside the biofilm and doing so without damaging skin cells.
This could mean that we might
have on our hands a new approach for therapy against biofilms in wounds. DNA is,
after all, the foundation of life itself - but it is also very encouraging to
know that we can now unlock its full potential as drug delivery for antibiofilm
We just might be on the
verge of witnessing the rise of the next action hero in the battle against
biofilms and antibiotic resistant bacteria.