Phage Therapy

Bacteriophages are viruses that selectively attack specific species of bacteria and are otherwise
harmless to animal cells, including humans. They were discovered 100 years ago by Frederick
W. Twort and Félix d’Hérelle and are distributed throughout Earth’s ecosystems and over a
broad bacterial host range, including bacteria naturally found in humans. It has been shown that
the attack of bacteriophages is specific, meaning that one species of bacteriophage targets only a
single species of bacteria (or even a specific strain of one species). The scenario of the attack is
as follows: (1) The bacteriophage attaches itself to a susceptible bacterium, exclusively infects
the host bacterial cell and (2) hijacks the bacterium’s biochemical machinery to produce multiple
copies of itself. (3) The bacterium then undergoes destruction (lysis) and new copies of the
bacteriophage are released and infect, exclusively, other bacteria of the same species in the
neighboring areas.

Despite this known interplay between bacteriophages and bacteria, research into bacteriophages
and their potential medical applications was largely abandoned for many years due to “The
Antibiotics Revolution.” Antibiotics were adopted as the main way of treating bacterial
infections due primarily to the fact that they are general purpose, as opposed to bacteriophages
that specifically target a single species of bacteria. Other advantages include the fact that
antibiotics are usually fast acting, efficient, and relatively cheap to manufacture. However, there
are several drawbacks as well to the use of antibiotics. One of these is that, unlike
bacteriophages, antibiotics can destroy beneficial bacteria in addition to harmful ones. More
importantly, the overuse of antibiotics can cause bacteria to evolve resistances to them, resulting
in antibiotic-immune “superbugs.”

The bacterial growth rate could potentially be reduced by the aerosol application of
bacteriophages. This can occur in a self-regulatory manner, similar to ecological prey–predator
regulation. The exponential growth of the bacteriophage population (limited primarily by the
population of the bacteria it preys on) should allow for a fast clearance, especially in cases where
the bacterial population has already grown significantly. The relationship can be described by
Lotka-Volterra or Kill-the-Winner population model.
Prophylactically administered bacteriophages reduced lung bacterial burdens and improved
survival of antibiotic-resistant S. aureus infected animals in the context of ventilator-associated
pneumonia. If needed, a selection of bacteriophages and optimal target bacteria could be quickly
identified by a group of experts as the species of bacteria that commonly cause respiratory
problems are well known and a bacteriophage that preys on a specific species can be quickly
identified by screening methods. If needed, quantitative microbiome sequencing could
potentially be used.

There are assumptions that need to be met during the clinical trials for the approach to work. (1)
The cohort has to be chosen to have a high probability of developing bacterial infections. (2) It
should be ensured to have the correct choice of bacteriophages that both target the optimal
bacteria candidates and are most effective at reducing that bacteria’s population growth. (3) The
bacteriophages should not interfere with the patient’s innate or adaptive immune system. (4) The
patient does not have antibodies toward bacteriophages used, nor develops any antibodies toward
bacteriophages to clear off the bacteriophage. (5) Another obstacle could be a risk of a species of
bacteria developing resistance to the bacteriophage, according to the co-evolutionary process.
However, this would be much less serious than the antibiotic resistance problem as it would only
reduce the effectiveness of that one bacteriophage and there is the possibility of the
bacteriophage also adapting to overcome any resistance to it. (6) Finally, bacteriophages are so
specific to one species of bacteria, and there is very little chance of the bacteriophage damaging
any beneficial bacteria, but this should still be verified in clinical trials.

Animal studies can help bridge the gap between in vitro studies and actual clinical application of
phage therapy. Unfortunately, most animal models investigate acute infections, which may not
be the ideal analog for phage therapy targeting chronic infections in humans. Many of these
studies observe best results when phage is applied simultaneously with the bacterial challenge,
which will not necessarily be applicable in the clinic. In many cases, no measures were taken to
check for the in vivo evolution of phage resistance by bacteria. Also, the comparison of phage
treatment to antibiotic treatment or even a combination of phage and antibiotic treatments is only
beginning to be investigated in animal models. Nevertheless, animal models provide vitally
useful data on efficacy and safety of phage therapy in living hosts and are crucial for further
development of the approach.

Systemic Infections

Several studies have investigated the efficacy of phage therapy for treatment of systemic
infections. The determinants of success for phage therapy to treat systemic infections are likely
dependent on multiple factors which need to be thoroughly examined prior to the widespread use
of phage as a treatment for sepsis in humans.

Local Infections

Phage therapy for localized infections (e.g., otitis, urinary tract infections, infected burns) is
recognized for its potential to entirely circumvent the use of chemical antibiotics. Furthermore,
use of chemical antibiotics for surgical and hospital-acquired infections is limited, as these often
constitute the strains with greatest antibiotic resistance.
Gastrointestinal Infections

Applying phage therapy to gastrointestinal bacterial infections could potentially reduce or

Lung Infections

Phage therapy for the treatment of lung infections, particularly chronic lung infections which are
common in those with cystic fibrosis (CF), has seen renewed interest recently with the increase
in MDR bacteria associated with the lung. Promising results for both prophylactic and curative
treatment of lung infections with phage indicate that these types of infections may be a reliable
target for effective phage therapy.

Antibiotic and Phage in Combination

While there have been many in vivo studies on the efficacy of phage therapy, not many recent
studies have compared the in vivo efficacy of phage therapy to that of antibiotics or even
combined phage and antibiotic treatment. As the future of phage therapy will likely be that of
combined therapy with chemical antibiotics, additional studies examining potential synergy
between phage and antibiotics both in vitro and in vivo are needed.

Question:

1. Prepare a scientific newsletter using information mentioned above. The newsletter must
contain an appropriate “Title”.

(Note: The above information is collected from scientific articles.)