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

Fan Yang, Alireza Labani-Motlagh, Josimar Dornelas Moreira, Danish Ansari, Jose Alejandro Bohorquez, Sahil Patel, Fabrizio Spagnolo, Jon Florence, Abhinav Vankayalapati, Ramakrishna Vankayalapati, John J. Dennehy, Buka Samten, Guohua Yi
doi: https://doi.org/10.1101/2023.01.23.525188
Fan Yang
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Alireza Labani-Motlagh
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
5Center for Discovery and Innovation, Hackensack Meridian Health, New Jersey
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Josimar Dornelas Moreira
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Danish Ansari
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Jose Alejandro Bohorquez
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Sahil Patel
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Fabrizio Spagnolo
2Life Sciences Department, Long Island University Post, Brookville, NY
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Jon Florence
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Abhinav Vankayalapati
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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Ramakrishna Vankayalapati
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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John J. Dennehy
3Biology Department, Queens College of The City University of New York, Flushing, NY
4The Graduate Center of The City University of New York, New York, NY
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  • For correspondence: Guohua.Yi@uthct.edu Buka.Samten@uthct.edu John.Dennehy@qc.cuny.edu
Buka Samten
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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  • For correspondence: Guohua.Yi@uthct.edu Buka.Samten@uthct.edu John.Dennehy@qc.cuny.edu
Guohua Yi
1Center for Biomedical Research, The University of Texas Health Science Center at Tyler
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  • For correspondence: Guohua.Yi@uthct.edu Buka.Samten@uthct.edu John.Dennehy@qc.cuny.edu
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Abstract

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 tested seven bacteriophage strains able to lyse Mycobacterium smegmatis for their Mtb-killing activities and found that four efficiently lysed Mtb H37Rv in 7H10 agar plates. However, only phage DS6A efficiently killed H37Rv in liquid culture and in Mtb-infected human primary macrophages. In subsequent experiments, we infected humanized mice with aerosolized H37Rv, then treated these mice with DS6A intravenously to test its in vivo efficacy. We found that DS6A treated mice showed increased body weight and improved pulmonary function relative to control mice. Furthermore, DS6A reduced Mtb load in mouse organs with greater efficacy in the spleen. These results demonstrated the feasibility of developing phage therapy as an effective therapeutic against Mtb infection.

Competing Interest Statement

The authors have declared no competing interest.

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Posted January 23, 2023.
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Bacteriophage therapy for the treatment of Mycobacterium tuberculosis infections in humanized mice
Fan Yang, Alireza Labani-Motlagh, Josimar Dornelas Moreira, Danish Ansari, Jose Alejandro Bohorquez, Sahil Patel, Fabrizio Spagnolo, Jon Florence, Abhinav Vankayalapati, Ramakrishna Vankayalapati, John J. Dennehy, Buka Samten, Guohua Yi
bioRxiv 2023.01.23.525188; doi: https://doi.org/10.1101/2023.01.23.525188
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Bacteriophage therapy for the treatment of Mycobacterium tuberculosis infections in humanized mice
Fan Yang, Alireza Labani-Motlagh, Josimar Dornelas Moreira, Danish Ansari, Jose Alejandro Bohorquez, Sahil Patel, Fabrizio Spagnolo, Jon Florence, Abhinav Vankayalapati, Ramakrishna Vankayalapati, John J. Dennehy, Buka Samten, Guohua Yi
bioRxiv 2023.01.23.525188; doi: https://doi.org/10.1101/2023.01.23.525188

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