Wow! The year 2019 sure went by quickly! I can't believe we're already seeing in 2020 this year. 🤓
One of our lab's (many!) successes this year was our involvement in the 2019 iPATH/VII Seminar series, co-hosted at UCSD by The Center for Innovative Phage Applications and Therapeutics and at SDSU by the Viral Information Institute. To sum up the many speakers we've had the privilege of listening to/conversing with, here's a summary of those talks (with links to those that were live streamed/recorded). This was originally published in the iPATH Quarterly Newsletter:
Seminar Series in Review
In a new marriage of basic and clinical science, the recently-initiated seminar series brought researchers together to share leading-edge insights into phage biology and phage-based therapeutics for infectious diseases. The monthly seminar series- Translational Research in Bacteriophage Therapies - is part of a joint effort between the University of California, San Diego (UCSD) Center for Innovative Phage Applications and Therapeutics (IPATH) and San Diego State University’s (SDSU) Viral Information Institute (VII). While the location alternated between the two institutes, most seminars were live streamed and now available for viewing on IPATH’s YouTube channel and center website.
Dwayne Roach, PhD Dwayne Roach, PhD from SDSU’s VII presented the inaugural seminar in March 2019 with his talk: “Lifesaving phage therapy does not work for everyone: How do we fix that?” His experimental study demonstrated that successful phage therapy depends on the host innate immune response, deemed “immunophage synergy.” In silico modeling indicated that host immunity was required to eliminate phage-resistant bacteria, while phage-resistant bacteria dominated the infection in immune deficient subjects. Whether such synergy also occurs in humans is not known, but should be studied.
Robert Schooley, MD In April, Robert “Chip” Schooley, MD, from UCSD and the Co-Director of IPATH, presented his seminar titled “Bacteriophage therapy: Moving from opportunistic observations to hypothesis driven research” as SDSU. He shared his experience treating Tom Patterson and others with compassionate-use phage therapy. Schooley noted that “phages end up where the money is”, or in other words, at the site of the infection. His emphasis on collaboration between the trifecta of research, advocacy, and clinical care made clear that in the future, this collaboration will be key to enabling and successful human clinical trials, which are urgently needed.
Graham Hatfull, PhD From the University of Pittsburgh, Graham Hatfull, PhD gave the first keynote presentation of the series with his talk entitled “Mycobacteriophages: Discovery, dynamics, collusion, and therapy.” In his take on the highly publicized Nature Medicine article, “Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus,” Hatfull reminded us of the many complexities involved with using phages from the lab and as human therapeutics, especially under the time pressure required to create a life-saving treatment. Indeed, meeting patient needs may require that some phages be engineered in the lab. The talk concluded with a discussion of a program that Hatfull started, the Science Education Alliance Phage Hunters Advancing Genomics and Evolutionary Science (SEA-PHAGES). Through this program, undergraduate students isolated and characterized phages for the University of Pittsburgh’s phage collection. After the seminar, Hatfull said, “it was wonderful to meet the teams of scientists and physicians at IPATH, and to discuss our common interests in bacteriophages and their potential therapeutic applications.”
David Pride, MD, PhD In June, David Pride, MD PhD from UCSD’s IPATH presented a talk titled “The role of bacteriophages in the human microbiome” at SDSU. He showed how phages persist within microbiomes over the course of time and how housemates share much of their microbiomes. Pride discussed how ecological investigation of microbial communities can change the way we approach microbiome engineering.
Katrine Whiteson, PhD Katrine Whiteson, PhD from the University of California, Irvine presented microbiome studies in July at SDSU in a talk titled “The coevolution of bacteriophages infecting Enterococcus from the human microbiome.” She discussed how predator-prey dynamics operate in the context of phage-bacteria interactions. For instance, phages isolated from sewage can be co-evolved to be more potent against a target bacterial pathogen. Whiteson showed a refined method of therapeutic cocktail design that employed co-evolution to improve synergies between phages in a cocktail.
Vincent Fischetti, PhD The second keynote speaker of the series, Vincent Fischetti, PhD from Rockefeller University, gave his talk in September at UCSD. In his talk, “Phage lysins as effective alternatives to antibiotics” he discussed how phage lysins can be used as an effective antimicrobial, alternative to using the whole phage particle. Lysins are enzymes produced by phages that kill bacterial cells by degrading a component of bacterial cell walls: peptidoglycan. Fischetti examined how phage lysins have entered into Phase III trials with the hopes that one day, lysins will be part of the standard of care in the hospital setting used to curb the spread of MRSA. Fischetti said, “(he) enjoyed his time meeting with the students and faculty” at both UCSD and SDSU and that he found the experience “scientifically very productive” and “learned a lot and hope(s) (that) the feeling was mutual”.
Justin Meyer, PhD The October seminar, presented at SDSU by Justin Meyer, PhD from UCSD, was titled “Darwin's entangled bank may hold the key to developing more effective bacteriophage therapeutics”. Through an evolutionary perspective, he showed that bacteria could attain a high level of antibiotic resistance with only a few mutations. Meyer shared experimental data and meta-analyses, suggesting that coevolving phages with the target bacterial pathogen prior to therapy should lead to more effective treatments because then the bacteria are less likely to evolve resistance to the phages that are further down the evolutionary path. Developing phages to infect both the “ancestral” phenotype as well as the predicted “new phenotype” is a novel approach to developing phage cocktails using phage-bacterial interaction networks.
Forest Rohwer, PhD Wrapping up the series for 2019 at UCSD, Forest Rohwer, PhD from SDSU presented his talk: “Which phage is a good phage?” in which he discussed the potential of phage therapies to activate potentially harmful prophages (endogenous latent viral infections) residing dormant within bacteria, which is also a concern with antibiotic therapies. Rohwer also showed a rapid pipeline for infection characterization in cystic fibrosis patient lungs that involves both the viral and bacterial dynamics, contributing to the design of safer phage therapies for clinical use.
iPATH and VII are ecstatic with the momentum of the seminar series, and look forward to new insights that 2020 will bring. Seminar time and location information can be found here.
By Tiffany Luong UCSD/SDSU PhD student San Diego State University