775
Review
www.expert-reviews.com ISSN 1478-7210 © 2011 Expert Reviews Ltd 10.1586/ERI.11.90
Bacteriophages (phages) are natural parasites of
bacteria that have long been considered as agents
for treating bacterial infections [1–4] . Phage ther-
apy, the use of phages as antibacterial agents, is
based on the fact that phages recognize, bind to
and multiply within bacterial host cells, rapidly
causing cell lysis. While early studies of phage biol-
ogy and therapy were unclear as to the nature of
bacteriophage – many thought them to be a com-
ponent of the human immune response or bacte-
rial enzymes [3] – phage therapy has nonetheless
been practised for approximately 90 years. Early
trials met with mixed results and the use of phage
therapy was never universally adopted [5,6] . With
the advent and eventual widespread use of antibi-
otics, phage therapy remained common practice
only in certain parts of the Soviet Bloc and Eastern
Europe, where it is still practised today.
Antibiotics interact with specific bacterial
cellular targets to produce selective toxicity.
However, the genes for these targets can be
changed through mutation and gene trans-
fer, and these mutations can become ampli-
fied in a population through natural selection.
While antibiotics are still successful in treat-
ing the majority of bacterial infections, there
are notable exceptions where frontline thera-
pies are no longer reliable [7–10] . Methicillin-
resistant Staphylococcus aureus (MRSA) [11] ,
vancomycin-resistant Enterococcus (VRE) [12] ,
and carbapenemase-producing strains of
Pseudomonas aeruginosa, Klebsiella pneumoniae
and Acinetobacter spp. [13,14] are just a few of
the bacteria which have driven the search for
alternatives to antibiotic use.
Recent reductions in the incidence of nosoco-
mial pathogens such as MRSA [15] and C. dif-
ficile [16] in the UK and several other countries
have been achieved by improved infection control
measures including better use of isolation and
barrier nursing, however rates of some Gram-
negative multi-antibiotic-resistant infections are
still on the increase and MRSA and C. difficile
remain major problems in some settings [17] . The
need for novel antimicrobial therapies therefore
remains high and indeed with the emergence
of panresistant strains of some Gram-negative
pathogens [18–20] it could be argued that the need
has never been greater since the pre-antibiotic era.
Against a background of increasing antibiotic
resistance and decreasing numbers of newly
licensed molecules [21] , the development of novel,
safe phage therapeutics appears attractive for a
number of reasons: they possess multiple mecha-
nisms of action that are separate from antibiotic
resistance mechanisms; they multiply at the
site of infection; usually have very narrow host
ranges with little or no effect on eukaryotic cells;
and they are readily isolated from a wide range
of environments.
Ben Burrowes
1
,
David R Harper
1
,
Joseph Anderson
1
,
Malcolm McConville
1
and Mark C Enright
†1
1
AmpliPhi Biosciences Corp., Colworth
Science Park, Sharnbrook,
Bedfordshire, MK44 1LQ, UK
†
Author for correspondence:
Tel.: +44 845 680 0971
Fax: +44 845 680 0972
mce@ampliphibio.com
The use of bacteriophages (phages) to treat bacterial infections, known as phage therapy, has
a history substantially longer than that of antibiotics, yet these drugs have been the treatment
of choice in the West for over 60 years owing to efficacy, low toxicity and ease of production.
Bacteria are becoming increasingly resistant to antibiotics while efforts to discover new agents
have drastically reduced. Phages have co-evolved with their hosts over billions of years and have
acquired mechanisms to counter bacterial defences such as extracellular biofilm production,
which severely reduces the effectiveness of conventional antibiotics. Recent animal and human
trials show phages to be safe, well-tolerated agents with a bright future as an alternative to
chemical agents.
KEYWORDS: antibioticresistance•antimicrobial•bacteriophage•bioflms•humantrials•phage
Bacteriophage therapy:
potential uses in the control of
antibiotic-resistant pathogens
Expert Rev. Anti Infect. Ther. 9(9), 775–785 (2011)
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