Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection

• DOI: 10.1016/j.cell.2022.04.024
• Publication Date: 2022-05-13T14:33:52Z
• Authors: Jerry A. Nick; Rebekah M. Dedrick; Alice L. Gray; Eszter K. Vladar; Bailey E. Smith; Krista G. Freeman; Kenneth C. Malcolm; L. Elaine Epperson; Nabeeh A. Hasan; Jo Hendrix; Kimberly Callahan; Kendra Walton; Brian Vestal; Emily Wheeler; Noel M. Rysavy; Katie Poch; Silvia Caceres; Valerie K. Lovell; Katherine B. Hisert; Vinicius Calado d...; Delphi Chatterjee; Prithwiraj De; Natalia Weakly; Stacey L. Martiniano; David A. Lynch; Charles L. Daley; Michael Strong; Fan Jia; Graham F. Hatfull; Rebecca M. Davidson
• Keywords: Mycobacterium abscessus; Phage therapy

Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages engineered enhance their capacity lyse M. selected specifically as the most effective against subject's bacterial isolate. In setting of compassionate use, evidence phage-induced lysis was observed using molecular metabolic assays combined clinical assessments. isolates pre post-phage treatment demonstrated genetic stability, general decline in diversity no increased resistance phage or antibiotics. anti-phage neutralizing antibody titers one time but did not prevent improvement throughout course treatment. subject received transplantation on day 379, systematic culturing explanted detect abscessus. This study describes associated markers successful advanced