Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child

Ameneh Khatami*, Ruby C.Y. Lin, Aleksandra Petrovic-Fabijan, Sivan Alkalay-Oren, Sulaiman Almuzam, Philip N. Britton, Michael J. Brownstein, Quang Dao, Joe Fackler, Ronen Hazan, Bri’Anna A. Horne, Ran Nir-Paz, Jonathan R. Iredell*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageAmerican English
Article numbere13936
JournalEMBO Molecular Medicine
Volume13
Issue number9
DOIs
StatePublished - 7 Sep 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Published under the terms of the CC BY 4.0 license.

Keywords

  • Pseudomonas aeruginosa
  • bacteriophage
  • child
  • immune response
  • osteoarticular infection

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