No matter how sophisticated implants, catheters, medical
devices or tissue engineering constructs are, bioilms are able to
form almost everywhere. Yet the bioilm state was notknown
when the majority of antibiotics were discovered, and as a result
all established antibiotics were based on studies of single bacteria.
However, eradication of the bacteria in bioilms requires antibi-
otic concentrations up to 1000-fold higher than single free-
living bacteria, and hence they can cause persistent and recurring
infections.
While antibiotics seemed to be able to cure every infectious
disease half a century ago, the current situation is devastating.
According to the federal Department of Health, Australia has
one of the highest rates of antibiotic use worldwide, with more than
23 million antibiotic prescriptions supplied to more than 45%
of Australians in 2013. The overuse and incorrect use of anti-
biotics in both humans and livestock can expose bacteria to
subtherapeutic concentrations of antibiotics, enabling bacteria
to evolve and adapt to existing antibiotic treatments. They are
now becoming increasingly resistant to last-resort antibiotics.
How can we battle these superbugs when established medical
care does not defeat them anymore?
One approach involves developing compounds whose mech-
anism of action is distinctively different from those of traditional
antibiotics. In tandem with this, novel compounds are also required
to tackle bacterial bioilms. These can kill the bacteria by attacking
and disrupting the thick slime layer so that treatments can enter
the fortress and ight against bacteria from the inside.
Another approach is to interfere with the ability of bacterial cells
to communicate with each other within the bioilm fortress,
enabling a streamlined and coordinated behaviour of the entire
bacterial community. If this signalling is interrupted, either by
degrading the signal molecules or interrupting the perception of
signals, the defence of the bacterial community against thera-
peutics would be weakened.
Another strategy is to block certain proteins and receptors on
the bacterial surface in order to attenuate bacterial virulence.
Small molecules, novel compounds in smart drug-delivery systems
and innovative coatings for medical devices offer the potential to
prevent attachment of bacteria, alter gene expression and inhibit
or disrupt bioilm formation.
A further approach is the therapeutic use of bacteriophages.
These viruses speciically target and ight single bacteria without
causing harm to the human body. Despite the huge potential of
phage therapy against multi-resistant superbugs, their use is contro-
versial and currently only approved in a handful of countries
worldwide. However, clinical trials taking place in Adelaide and
other cities around the world might open the use of this new
therapy in the near future.
Another novel treatment targets bacterial metabolism. In
particular, the metabolism of iron is vital for bacterial growth,
survival and pathogenesis.
My research has identiied a novel treatment combining two
compounds that work synergistically together. The irst
compound captures nutrients in the environment around
bioilms, thereby cutting off essential food paths for the bioilm
fortress and leading to its starvation. Subsequently, the bioilm
opens speciic gates in order to allow nutrient sources into the
fortress. The second compound in my strategy is a “Trojan
horse” that mimics a preferred food source of bacteria but has
bioilm-killing properties. When this is allowed to enter the
fortress, bioilms can be conquered and bacteria defeated.
With this new treatment I am speciically looking at how
to combat chronic sinus infections. Chronic sinusitis is highly
prevalent in the community, affecting one-sixth of Australians
irrespective of gender, nationality or age. The available thera-
pies are mainly based on long-term treatment with antibiotics,
but many people suffer from recurrent sinus infections due to
antibiotic-resistant superbugs. Surgery is often the only remedy
for the treatment of chronic sinusitis.
To avoid relapse due to bacteria hiding in the bioilm, I have
developed a drug-delivery-system that releases the two
compounds at the site of infection, so bacteria starve and die.
The treatment is topically applied in the sinuses rather than
taken as a tablet. This produces fewer side-effects, less systemic
effects throughout the body and less interactions with other
compounds or food. Essentially, as this novel treatment does not
rely on traditional antibiotics, we have not encountered any
bacterial resistance yet.
So far my results have been very promising and show that this
approach is an eicient and safe way to kill bacteria in their
bioilm fortress. The University of Adelaide’s Ear Nose and
Throat Surgery Department is proposing The Queen Eliza-
beth Hospital as the base for the irst human trials.
While the current focus is on chronic sinusitis, a successful
clinical trial will hopefully lead us to further reine the treatment
so it can eventually be used to treat people suffering from a
broad range of chronic infections.
Katharina Richter is a PhD candidate in the Departmentof Ear, Nose and Throat Surgery, Basil
Hetzel Institute for Translational Health Research & The Queen Elizabeth Hospital, The
University of Adelaide.JUNE 2016|| 19Australia has one of the highest rates of antibiotic use worldwide, with
more than 23 million antibiotic prescriptions supplied to more than 45%
of Australians in 2013.