Bacteriophage cocktail reduces bacterial load in disease challenge

Recent studies examining the use of phage technology​ in mastitis challenges caused by E.coli or Staphylococcus aureus​ (Staph aureus​) have demonstrated the potential effectiveness of the bacteriophage technology, said Heather Bessoff, director of sales, marketing and business development with EpiBiome.

One of the studies also offered a look at how a cocktail of bacteriophages preformed when used with a target species.

“The Staph [research] also has other applications – it’s the causative agent for lots of different infection including [some in people],​” she told FeedNavigator. “This helps lead us to the conclusion that the phage technology could be helpful for treatment in people and animals, and the E.coli does help us in understanding human E.coli infections.”​

Both recent studies involved the use of mixes or cocktails of bacteriophages, she said. Individually, bacteriophages can be specific about which strain of a bacteria they address, by using a combination, the goal was to expand the potential for the technology to be effective.  

“The way we approach it is we look for what are the most prevalent circulating strains of the bacteria and then develop cocktails that are designed to be effective against the broadest range of circulating bacteria,”​ she said. “We’re trying to make the cocktails that are most relevant.”​

The California-based biotech company is starting with work on mastitis because the disease is the primary reason that dairy cattle are treated with antibiotics, said Bessoff. “In an era where we need to be mindful of how we use antibiotics, it was a good opportunity to apply an alternative to antibiotics to treat a prevalent disease in dairy cows,”​ she added.

“We’ve actually looked at applications for phage cocktails across all species, and where are the biggest unmet needs, and there are certainly many opportunities,” ​she said. “But for a small, start-up company we have to be more focused.”​

In addition to study work, the company has recently announced funding awards from TechAccel and Stanford’s StartX.

Mastitis research details​

The studies examined different bacteria – E.coli or Staph aureus​ – that can cause separate forms of mastitis, said Bessoff. “Mastitis is the general disease – and multiple bacteria [types] cause different forms of the disease,”​ she added.

“We have an ongoing project in dairy cattle mastitis developing an alternative to antibiotics,”​ she said. The two projects looking at improving animal response to the disease challenge involved the use of bacteriophage cocktails designed to address E.coli or Staph aureus​ – two common causes of mastitis.

In the dairy cow study, 16 cows were infected with E.coli, she said. Eight of the challenged cows received a bacteriophage cocktail designed to address multiple strains of the E.coli bacteria and eight were not.

The cocktail was offered six hours after the disease challenge, she said. Bacteria counts present in the milk were then collected and measured for multiple time-periods.

After 12 hours the researchers found a 2.5log reduction in counts of E.coli bacteria, said Bessoff. Or, a drop of about 99.7% compared to the control group cows.

“Cows are able to mount a pretty significant immune response to some types of mastitis, including E.coli. The majority of cows self-cure and E.coli infection, but those that don’t can get really, really sick,” ​she said. “After the 12 hours there was still a difference [between cow groups,] but the immune system starts to kick in.”​

Overall, cows getting the bacteriophage cocktail saw bacteria disappear more quickly and the amount present stayed lower, she said.

At this point, the cocktail needs formulation work, followed by additional trials and development, said Bessoff.

The study done to address Staph aureus​ involved use of a designed cocktail of bacteriophages to lactating mice that had been challenged with Staph aureus​, she said. The groups of animals included a negative control that were challenged with Staph aureus​ but that was not given the bacteriophage mix, a positive control that was infected and offered an antibiotic, and an infected group that received the bacteriophage mix.

Results for the positive control demonstrated that the antibiotic was quite effective, she said. The mice getting the bacteriophages had similar results.

There was a “rescue”​ of the infected tissue for mice that receive either product, she said. The tissue was able to return to a healthy state.

“For Staph aureus and the E.coli mastitis program we are actively looking for strategic partners to help us develop those products,”​ she said.

New funding sources​

The work with TechAccell has provided an investment to the biotech company, said Bessoff.

TechAccel is a company that seeks to fund science advancement projects and invest in new technologies, EpiBiome said. Stanford-StartX is a non-profit that works with entrepreneurs and offers education and mentoring.

“[The company] has provided us funding for further development,”​ said Bessoff. “There are some agricultural-based studies and funding for general scientific advancement.”

The work with Stanford StartX has provided some funding for additional work, she said. But it also offers about 16 months of mentorship, which is ongoing.