Host and pathogen response to bacteriophage engineered against Mycobacterium abscessus lung infection
Open accessAbstract
Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.
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Lysogeny and horizontal gene transfer pose theoretical risks, as some phages can integrate into bacterial genomes and potentially transfer antibiotic resistance or virulence genes.
“Lysogeny and horizontal gene transfer pose theoretical risks, as some phages can integrate into bacterial genomes and potentially transfer antibiotic resistance or virulence genes.”
From Phage therapy in oncology: opportunities for cancer prevention and treatment (2026) · cites this paper as [149]
The Introduction states that most phages infecting M. abscessus are temperate and can integrate into bacterial genomes, supporting the lysogeny risk. The paper does not say that phages may transfer antibiotic-resistance or virulence genes through horizontal gene transfer. The Results instead report no viral-DNA incorporation in the isolates studied; that finding does not rule out a theoretical risk elsewhere. (LLM, conf=0.87)
Experimental — accuracy not yet measuredPhages have been successfully used to treat chronic, drug-resistant infections of M. abscessus.
“successfully used to treat chronic, drug-resistant infections of M. abscessus (177–179)”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [179]
Phages have been explored as diagnostic tools.
“Phages have also been explored as diagnostic tools, and successfully used to treat chronic, drug-resistant infections of M. abscessus (177–179).”
From Mycobacterium smegmatis: The Vanguard of Mycobacterial Research (2023) · cites this paper as [179]
The Results section, “Identification of Phages Active Against M. abscessus” (page not provided), describes screening a patient’s bacterial isolate to select therapeutic phages. The Methods describe phage-susceptibility and antibody assays, but neither those passages nor the passages retrieved for diagnostic use say that phages were explored as diagnostic tools. (LLM, conf=0.74)
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- Authors
- Nick, J. A., Dedrick, R. M., Gray, A. L., Vladar, E. K., Smith, B. E., Freeman, K. G., Malcolm, K. C., Epperson, L. E., Hasan, N. A., Hendrix, J., Callahan, K., Walton, K., Vestal, B., Wheeler, E., Rysavy, N. M., Poch, K., Caceres, S., Lovell, V. K., Hisert, K. B., de Moura, V. C., Chatterjee, D., De, P., Weakly, N., Martiniano, S. L., Lynch, D. A., Daley, C. L., Strong, M., Jia, F., Hatfull, G. F., & Davidson, R. M.
- Affiliations
- National Jewish Health (US)
- University of Pittsburgh (US)
- University of Colorado Anschutz (US)
- Colorado State University (US)
- Children's Hospital Colorado (US)
- Corresponding author
- Nick, Jerry A.
- Hatfull, Graham F.
- ORCID
- Nick, Jerry A.
- Dedrick, Rebekah M.
- Gray, Alice L.
- Vladar, Eszter K.
- Smith, Bailey E.
- Freeman, Krista G.
- Malcolm, Kenneth C.
- Epperson, L. Elaine
- Hasan, Nabeeh A.
- Hendrix, Jo
- Walton, Kendra
- Vestal, Brian
- Rysavy, Noel M.
- Poch, Katie
- Caceres, Silvia
- Lovell, Valerie K.
- Hisert, Katherine B.
- Chatterjee, Delphi
- De, Prithwiraj
- Martiniano, Stacey L.
- Lynch, David A.
- Daley, Charles L.
- Strong, Michael
- Hatfull, Graham F.
- Davidson, Rebecca M.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2022-05
- Volume
- 185
- Issue
- 11
- Pages
- 1860-1874.e12
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC9840467
- OpenAlex
- W4280519382
- Cited by
- 251
- References
- 64
- Citations by year
- 2026: 39 · 2025: 60 · 2024: 70 · 2023: 50 · 2022: 32
- FWCI
- 28.24
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute (K01-AI125726, GT12053)
- University of Colorado Denver
- Cystic Fibrosis Foundation (NICK20Y2-OUT, MALCO19I0, NICK20Y2-SVC, NICK17K0, NICK18P0, HATFUL19GO)
- National Jewish Health
- National Institutes of Health (R35 GM131729)
- Topics
- Physical Sciences › Environmental Science › Ecology › Bacteriophages and microbial interactions
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Keywords
- Mycobacterium abscessus, phage therapy, phage engineering, cystic fibrosis lung disease, pulmonary infection, phage resistance, lung transplantation, compassionate use
- MeSH terms
- Mycobacterium abscessus, Anti-Bacterial Agents, Bacteriophages, Cystic Fibrosis, Humans, Lung, Male, Mycobacterium Infections, Nontuberculous
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