The first technique, called tube capturing, involves capturing – not
killing – S. aureus cells using a modified medical tube coated with
polyclonal antibodies (pAb). Both ends of the tube are immersed into a
solution of whole human blood with S. aureus pathogens added. The
blood-bacteria solution circulates through the tube for 5 hours,
allowing the pathogens to adhere to the antibodies on the inner surface
of the tube, thus removing them from the blood. This technique captured
83.4% of the bacteria. In a paper published in Nature in 2017,
Vinerean et al. [2] employ the same
technique in vivo using rats induced with the S. aureus infection,
resulting in a 99.1% capture. They further confirm its feasibility by
capturing the food pathogen, Salmonella typhimurium , in
ground chicken and beef. A second method, photodynamic therapy technique (PDT), requires a
conjugate of the polyclonal antibody and a photosensitizer, Chlorin E6
(Ce6). A photosensitizer is a light-sensitive molecule that elicits
chemical changes in another molecule. The Ce6-pAb conjugate attaches to
the pathogens in the blood-bacteria sample circulating through a
modified tube, and is activated by a near infrared light, killing the
pathogens. Results of this experiment show a 71.4% reduction in the
number of pathogens.
Ultraviolet irradiation is commonly used to kill bacteria and viruses in
surgical wounds, drinking water and wastewater treatment. In this
experiment, the blood-bacteria sample circulates through a tube passing
through an illumination chamber with mirrored walls. UV light
illuminates chamber, destroying 61.6% of the pathogens in this case. A
plausible explanation for this relatively low result is the absorption
of ultraviolet light by haemoglobin in the blood. Haemoglobin absorbs
most of the UV light [3], meaning only the
pathogens at the surface of the tube get exposed and die. Tube capturing is evidently the most effective out of the three in
reducing bacteria count. However, as it does not actually kill bacteria,
it would be more beneficial to use it with another technique to prevent
repopulation of the uncaptured bacteria. Combining PDT with tube
capturing eliminated 87.1% of pathogens, while a UV-tube capturing
configuration was more effective, eliminating 89% of bacteria. Using
the three methods together was the most successful, reducing the
bacteria count by 92%.
Although this research is highly promising, it raises a crucial
question. How safe would these techniques be for humans? According to
the paper [1], having excess
photosensitizer-antibody conjugates in the blood stream pose a potential
risk. In the experiment, the sample goes through a wait time where the
blood circulates without NIR light for the first 2 hours, giving
sufficient time for all the conjugates to bind to pathogens. A similar
technique would be followed in humans and animals, allowing enough
binding between conjugates and target cells, and the unbound conjugates
would be cleared out by the body’s natural filtering organs. Further
tests are required to determine the appropriate wait time that would
maximise efficiency of the process while keeping collateral damage to a
minimum. Techniques such as complete blood counts can be carried out to
quantify the death of targeted and non-targeted cells.
Despite the widespread application of ultraviolet irradiation for
germicidal purposes, health risks such as skin cancer have caused
limitations to its use in humans. However, UV light is non-specific,
which is advantageous as it clears out most microorganisms. Its effects
on other blood components are unknown and would need to be investigated
before this technique can be used to kill pathogens in human blood. There is still considerable room for improvement. For instance,
additional types of antibodies or binding molecules can be used to
create more binding sites and reduce competition. Bioengineering
solutions are being developed, which will cater to larger throughputs of
blood from humans and other animals. Also, further tests will use
binding molecules that target a wide variety of pathogens, thus
eliminating the need to identify the pathogen beforehand. Future
experiments can extend the use of these techniques to target parasites,
fungi, viruses and other microorganisms using suitable binding
molecules.
The significance of this study is immense. Kim & Gaitas’ work provides
possible solutions to the uncertainty of a future without antibiotics.
As resistance spreads more rapidly, it is imperative that we direct our
focus to other forms of treatment. These novel techniques would be
especially suitable for individuals with antibiotic allergies or
immunocompromised patients with diseases such as cancer or HIV. Although
many patients may not appreciate the idea of treating bacterial
infections by getting wired to a machine while their blood gets pumped
through tubes, circumstances may require these seemingly cumbersome
treatments in the near future. However, with constant advancements in
science and biotechnology, these techniques – and others to come –
will eventually be optimized for the suitability of patients.
Angelo Gaitas and Gwangseong Kim are in
the Department of Electrical and Computer Engineering, Florida
International University.