Wednesday, 19 November 2014

Phage Therapy

Principles of Molecular Virology Principles of Molecular Virology, Chapter 6 (Virus Infection), discusses not only the treatment of virus infections, but also how viruses can be used to treat infections.

Phage therapy, the use of bacteriophages to treat or prevent disease, stretches back nearly a century to the earliest days of the discovery of phages. Long before the discovery of antibiotics, the thought that viruses which lyse bacteria could be used to treat diseases was highly attractive. Soon after the discovery of bacteriophages by Frederick Twort (1915) and Felix d'Hérelle (1917), treatment of bacterial infections in humans was tried. This reference gives a good overview of the advantages and the disadvantages of this approach.

Loc-Carrillo C., and Abedon S.T. (2011) Pros and cons of phage therapy. Bacteriophage 1(2): 111–114. doi: 10.4161/bact.1.2.14590
Many publications list advantages and disadvantages associated with phage therapy, which is the use of bacterial viruses to combat populations of nuisance or pathogenic bacteria. The goal of this commentary is to discuss many of those issues in a single location. In terms of "Pros," for example, phages can be bactericidal, can increase in number over the course of treatment, tend to only minimally disrupt normal flora, are equally effective against antibiotic-sensitive and antibiotic-resistant bacteria, often are easily discovered, seem to be capable of disrupting bacterial biofilms, and can have low inherent toxicities. In addition to these assets, we consider aspects of phage therapy that can contribute to its safety, economics, or convenience, but in ways that are perhaps less essential to the phage potential to combat bacteria. For example, autonomous phage transfer between animals during veterinary application could provide convenience or economic advantages by decreasing the need for repeated phage application, but is not necessarily crucial to therapeutic success. We also consider possible disadvantages to phage use as antibacterial agents. These "cons," however, tend to be relatively minor.

Phage Therapy Yet after the initial enthusiasm, this idea has never become a widespread practical reality. Devotees of phage therapy defend their cherished belief with almost religious fervor, but there are serious obstacles to be overcome, such as the narrow host range of most phages (a few strains of bacteria, not even an entire species) and the speed at which bacteria develop resistance to infection. An entertaining account is given by William Summers:

"The history of phage therapy, since the discovery of phages a century ago, has been fraught with conflicting observations, misinterpretations, and incomplete understanding, all of which are part of normal science. But there is more: the history of phage therapy is rich with politics, personal feuds, and unrecognized conflicts. Understanding these extra-scientific aspects of its history can help explain the tortuous course of phage therapy over the past century."
Summers, W.C. The strange history of phage therapy. (2012) Bacteriophage. 2(2): 130–133. doi: 10.4161/bact.20757

As the spectrum of clinically useful antibiotics dwindles in the face of an ever increasing number of multiple-resistant "superbugs", phage therapy increases in attractiveness, but is unlikely ever to replace the antibiotic golden era of disease treatment we are now leaving behind. There are some particular areas where the concept is especially interesting - tackling biofilms for example. Bacteria embedded in the matrix of a biofilm are often more resistant to antibiotic treatment than free "planktonic" baceria. As the significance of biofilms increases with the rise of medical devices, this is an area where phage therapy is worth investigating.

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