For the first “field trip” of the new year, the Roach Lab adventured to UCSD for the re-instatement of the IPATH “Translational Research in Bacteriophage Therapies” seminar series. Co-hosted by Dr. David Pride (UCSD, IPATH talk in 2019) and Dr. Katrine Whiteson (UCI, IPATH talk in 2019), the series has been on a three-year hiatus amid COVID19 and other happenings around the world. We’re so excited to once again meet in-person and learn more about phages from this series!
Dr. Daria Van Tyne from the University of Pittsburgh gave the first talk of the 2023 series titled, “Functional genomics and phage therapy for antibiotic-resistant bacterial infections”. Her research group studies “how bacteria evolve to become superbugs, using comparative genomics and functional analysis”.
Dr. Van Tyne discussed two phage therapy cases that her group has led at UPMC.
First, a 32 year-old CF patient with B. multivorans bacteremia was treated using a combination of phages and antibiotics. The patient had been chronically colonized with the pathogen since at least 2001. Following a double lung transplant in 2017, the patient was admitted to the hospital in Fall 2020 with MDR B. multivorans. Impressively, this case highlighted how quickly phages could be identified and formulated for phage therapy. In this case it only took 10 days! (By collaborator Dr. Ben Chan.) Unfortunately, the patient only experienced transient improvement before transitioning to comfort care. A single phage BCh7 was both inhaled (7 days) and given intravenously (1 day) concomitant with antibiotics. Dr. Van Tyne then discussed results from patient samples collected. qPCR was used to track changes in bacterial and phage abundance over time, showing a decrease in B. multivorans in the days following phage initiation as well as what looks like phage amplification on day 6 of treatment. This case report is now under review for publication, but it’s certainly exciting to see these promising phage-focused results from only 8 days of treatment. The case has also led to new work in the Van Tyne lab looking at the possibility of sourcing prophages from Burkholderia for therapeutic phage candidates.
Next, Dr. Van Tyne discussed a second phage therapy case for a 50 year-old patient with E. faecium bacteremia. The patient underwent several failed courses of IV antibiotics before being referred for phage therapy in Fall 2020. A single phage (9184, from the Duerkop Lab) was identified against the isolates and given orally and intravenously. The bacteremia surprisingly cleared immediately this time! The patient’s continued outpatient phage treatment seemed to improve her quality of life despite several bouts of recurrence with milder symptoms. A second phage was added in April 2021 to try to control the infection, but unfortunately therapy was eventually withdrawn. Dr. Van Tyne walked us through a really fascinating series of shotgun metagenomic findings that illustrated changes in E. faecalis and E. faecium over time that correlated with changes in the patient’s antibiotic and phage treatment regimen. This data really illustrated the impact that phages had on the patient’s E. faecium colonization over time. Overall, the case made for a really interesting look at the effects of long-term phage and antibiotic treatment impacted the patient’s recurrent infection for >1 year. The pre-print for this work is available here.
As a phage therapy enthusiastic this case was certainly rich with interesting findings and promising work! The full talk is available on YouTube for those interested.
After the talk we took a stroll around UCSD with our new lab additions, Nino (visiting from the Eliava institute in Georgia), Luke (our new bioinformatics master’s student), and Johann (rotation student in the CMB JDP program).
We look forward to future IPATH talks!