Open AccessBacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child
Author(s) -
Khatami Ameneh,
Lin Ruby C Y,
PetrovicFabijan Aleksandra,
AlkalayOren Sivan,
Almuzam Sulaiman,
Britton Philip N,
Brownstein Michael J,
Dao Quang,
Fackler Joe,
Hazan Ronen,
Horne Bri’Anna,
NirPaz Ran,
Iredell Jonathan R
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202113936
Subject(s) - innate immune system , phage therapy , adjunctive treatment , downregulation and upregulation , immune system , pseudomonas aeruginosa , immunology , acquired immune system , immunity , biology , transcriptome , microbiology and biotechnology , medicine , bacteriophage , bacteria , gene , gene expression , genetics , escherichia coli , biochemistry
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.