Clinical bacteriophage therapy in the 21st century

Morales S

AmpliPhi Biosciences.

It is now unanimously accepted that the world has entered a dangerous phase in the treatment of multi-resistant bacterial infection. The problem seems to be that the speed and ability of the bacterial community to develop resistance far exceeds the capacity of the biomedical and scientific community to develop new antibacterials. Faced with this situation is it perhaps time to acknowledge that the current antibiotic paradigm, if not broken, is in need of review, and that new alternative treatment options are urgently needed. A new antibacterial treatment would ideally have the capability of matching, and if possible exceeding the mutation rate of the bacterial targets. In other words, a form of intelligent antibacterial that out-mutates the mutators. Bacteriophage therapy, the use of highly specific bacterial viruses to treat bacterial infections, is one alternative with the potential to achieve this. Historically, bacteriophages (phages) were discovered 100 years ago at the Pasteur Institute in Paris. The therapy was widely practised until the middle of last century, until the advent of small molecule antibiotics such as penicillin saw the practise fade into obscurity for the next 50 years, before a major renaissance in the late 1990s. This talk will concentrate on the extensive progress made since that time in understanding the biology of phages and their potential for clinical application. The results from both pre-clinical and human clinical trials will be discussed, along with the issues facing the fledgling phage therapy industry such as production, regulatory and financial constraints. Exciting new developments in the combined use of phages and antibiotics will be described which offer the tantalising possibility that phage therapy might not only be able to contain antibiotic resistant bacteria but even reverse it.