Bacteriophage therapy for the treatment of Mycobacterium tuberculosis infections in humanized mice

The continuing emergence of new strains of antibiotic-resistant bacteria has renewed interest in phage therapy; however, there has been limited progress in applying phage therapy to multi-drug resistant Mycobacterium tuberculosis ( Mtb ) infections. In this study, we show that bacteriophage strains...

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Published in:Communications biology 2024-03, Vol.7 (1), p.294-13, Article 294
Main Authors: Yang, Fan, Labani-Motlagh, Alireza, Bohorquez, Jose Alejandro, Moreira, Josimar Dornelas, Ansari, Danish, Patel, Sahil, Spagnolo, Fabrizio, Florence, Jon, Vankayalapati, Abhinav, Sakai, Tsuyoshi, Sato, Osamu, Ikebe, Mitsuo, Vankayalapati, Ramakrishna, Dennehy, John J., Samten, Buka, Yi, Guohua
Format: Article
Language:English
Subjects:
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Animals
Antibiotic resistance
Biomedical and Life Sciences
Body weight
Drug resistance
Humans
Life Sciences
Liquid culture
Macrophages
Macrophages - microbiology
Mice
Multidrug resistance
Mycobacterium tuberculosis
Phage Therapy
Phages
Respiratory function
Spleen
Strains (organisms)
Tuberculosis
Tuberculosis - microbiology
Tuberculosis - therapy
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Summary:The continuing emergence of new strains of antibiotic-resistant bacteria has renewed interest in phage therapy; however, there has been limited progress in applying phage therapy to multi-drug resistant Mycobacterium tuberculosis ( Mtb ) infections. In this study, we show that bacteriophage strains D29 and DS6A can efficiently lyse Mtb H37Rv in 7H10 agar plates. However, only phage DS6A efficiently kills H37Rv in liquid culture and in Mtb -infected human primary macrophages. We further show in subsequent experiments that, after the humanized mice were infected with aerosolized H37Rv, then treated with DS6A intravenously, the DS6A treated mice showed increased body weight and improved pulmonary function relative to control mice. Furthermore, DS6A reduces Mtb load in mouse organs with greater efficacy in the spleen. These results demonstrate the feasibility of developing phage therapy as an effective therapeutic against Mtb infection. Bacteriophage strain DS6A efficiently eradicates intracellular Mtb in human macrophages, while humanized mice treated with DS6A show improved pulmonary function and reduced Mtb load in mouse organs with greater efficacy in the spleen.
ISSN:2399-3642
2399-3642
DOI:10.1038/s42003-024-06006-x