RT Journal Article SR Electronic T1 Bacteriophage therapy for the treatment of Mycobacterium tuberculosis infections in humanized mice JF bioRxiv FD Cold Spring Harbor Laboratory SP 2023.01.23.525188 DO 10.1101/2023.01.23.525188 A1 Fan Yang A1 Alireza Labani-Motlagh A1 Josimar Dornelas Moreira A1 Danish Ansari A1 Jose Alejandro Bohorquez A1 Sahil Patel A1 Fabrizio Spagnolo A1 Jon Florence A1 Abhinav Vankayalapati A1 Ramakrishna Vankayalapati A1 John J. Dennehy A1 Buka Samten A1 Guohua Yi YR 2023 UL http://biorxiv.org/content/early/2023/01/23/2023.01.23.525188.abstract AB 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 StatementThe authors have declared no competing interest.