Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child
Ameneh Khatami, Ruby C.Y. Lin, Aleksandra Petrović Fabijan, Sivan Alkalay‐Oren, Sulaiman Almuzam, Philip N Britton, Michael Brownstein, Quang Dao, Joe Fackler, Ronen Hazan, Bri’Anna Horne, Ran Nir‐Paz, Jonathan R. Iredell
Abstract
Adjunctive phage therapy was used in an attempt to avoid catastrophic outcomes from extensive chronic Pseudomonas aeruginosa osteoarticular infection in a 7-year-old child. Monitoring of phage and bacterial kinetics allowed real-time phage dose adjustment, and along with markers of the human host response, indicated a significant therapeutic effect within two weeks of starting adjunctive phage therapy. These findings strongly suggested the release of bacterial cells or cell fragments into the bloodstream from deep bony infection sites early in treatment. This was associated with transient fever and local pain and with evidence of marked upregulation of innate immunity genes in the host transcriptome. Adaptive immune responses appeared to develop after a week of therapy and some immunomodulatory elements were also observed to be upregulated.