Viruses that kill bacteria - bacteriophages - offer an alternative to antibiotics in treating bacterial infection. One company which is developing such anti-infectives is San Francisco-based biotech Epibiome, but according to CEO Nick Conley this is just one of a number of alternative therapies to antibiotics needed to combat the danger posed by bacterial resistance.
“There is no single solution,” he told Biopharma-Reporter.com. “[Bacteriophages] represent the most specific technology for eliminating bacteria that is known… [but] are one piece of an arsenal that will likely also include bacteriocins (peptides and R-type pyocins), lysins, bacteria-sensitising and quorum-sensing molecules, live biotherapeutics, and even small-molecule antibiotics.”
Bacterial resistance in spreading. Earlier this year, resistance to the "last resort" antibiotic Colistin was detected in the US for the first time, 12-months after it emerged in China.
Despite this, drug industry investment in the development of alternatives over the past few years has been minimal according to Conley, who does not expect the situation to change until a crisis point is reached.
“Expect R&D investment when, like cancer, most people know someone who died unexpectedly of an antibiotic-resistant infection. That will help garner media attention, but even that isn't the real concern. The real concern is that we lose access to the last 100 years of surgical advances because the risk of post-operative infection outweighs the benefit of the procedure,” he said.
“If the situation continues at current trends, the only invasive procedures that will be performed are the ones that prevent imminent death, and that could happen in our lifetimes. Antibiotic resistance--not terrorism, global warming, or nuclear warfare--is the most imminent threat to humanity today.”
Epibiome has its own platform for high-throughput phage discovery and characterization and, for manufacture, uses a bioreactor containing a large concentration of the host bacteria, which is then seeded with phages.
“In each infection event that ensues, a phage binds to specific receptors on the surface of the bacterium, hijacks its cellular machinery, and uses it to make somewhere between about 10 and 100 copies of itself which burst out at the end of the lytic cycle.”
He added the number of phages increases very quickly until there are no more bacteria in the reactor, with the process taking less than an hour.
“After that, we have a series of purification steps to remove toxins and host-cell proteins and isolate the phages.”
Behind the Iron Curtain
Anti-infective therapies based on bacterial viruses was fairly standard in Eastern Europe and Soviet Russia but until now was largely ignored by the West.
This was due to penicillin, said Conley. “At the time, the only good bacterium was a dead one, and it didn't make sense to deliver a bacteria-specific virus if you could give someone penicillin and kill everything.
“The Soviets were behind the ‘Iron Curtain,’ so they didn't have access to small-molecule antibiotics research in the US in the earliest days. Accordingly, they continued using phages for human therapy, which were part of standard military rations if you fought in Stalin's Red Army.”
Microbiome is today one of a number of Western firms looking at anti-infective therapies based on bacterial viruses - Ampliphi Biosciences being another, and Conley said his firm is exploring partnerships with several larger companies.
“In many respects, the West has caught up, but it is important to realise that the Soviets were the pioneers, and they deserve a lot of credit for this.”
However, “due to technology limitations, their approach was very empirical: Culture a bacteria from a patient, screen a collection of phages to find one or more that kill it, and deliver those phages to the site of the infection. This has some pretty obvious scaling limitations and doesn't fit within treatment paradigms in Western medicine.”