{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:54:11Z","timestamp":1792079651723,"version":"4.4.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:00:00Z","timestamp":1792022400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Phage therapy offers promise to combat antimicrobial resistance, including drug-resistant tuberculosis. Understanding phage activity against Mycobacterium tuberculosis (Mtb) in granuloma-like microenvironments that induce non-replicating states, characterized by hypoxia and acidity, is essential.<\/jats:p>\n <\/jats:sec>\n \n Objectives<\/jats:title>\n To evaluate a phage combination against Mtb under hypoxic, acidic (pH 5.5), and stationary-phase conditions in vitro.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n Mtb H37Rv cultures were grown to exponential phase for time-kill studies (106 colony forming units (CFU)\/mL) under normal, hypoxic, and acidic conditions. Hypoxia was generated using sealed containers with gas sachets. Stationary-phase cultures were grown for 14\u201321 days and used undiluted. Treatments included control media, single phages (Fred313cpm-1\u039433, Fionnbharth\u039445\u039447and Muddy HRM N0157-2), phage combination (multiplicity of infection 10:1), and rifampicin or isoniazid (0.1\u2005\u00b5g\/mL each). Phage titers (measured using M. smegmatis overlays) and bacterial counts (CFU on Middlebrook 7H11) were assessed at repeated time-points. Longitudinal phage-bacteria dynamics mixed-effects modelling and simulation was performed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n In actively growing cultures, phage levels rose by day 7, followed by sustained reductions in Mtb counts over 31 days. Phages prevented regrowth seen with antibiotics alone. Acidic conditions variably affected individual phage stability and activity. Under hypoxic and stationary conditions, phage titers remained stable, but no reduction in Mtb was observed. Model-based predictions adequately captured phage-mycobacterial interactions with and without rifampicin.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Productive lytic activity was not observed in assays with non-replicating mycobacteria. Established models can support future experimental designs. This study provides mechanistic insights driving progress in the field of phage therapy development.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/infdis\/jiag516","type":"journal-article","created":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T11:26:21Z","timestamp":1791804381000},"source":"Crossref","is-referenced-by-count":0,"title":["Activity of a three-phage combination against\n Mycobacterium tuberculosis<\/i>\n in disease-relevant conditions"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0966-3233","authenticated-orcid":false,"given":"S","family":"Janssen","sequence":"first","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Community for Infectious Diseases & Research Institute of Medical Innovation , Nijmegen ,","place":["The Netherlands"]},{"name":"TASK , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S E","family":"Larsen","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Center for Global Infectious Disease Research , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M Pozuelo","family":"Torres","sequence":"additional","affiliation":[{"name":"Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0464-5189","authenticated-orcid":false,"given":"M","family":"Beldjenna","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , Pittsburgh ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7256-5188","authenticated-orcid":false,"given":"C A Guerrero","family":"Bustamante","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine, Department of Pediatrics , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Florian","sequence":"additional","affiliation":[{"name":"University of Washington, Department of Global Health , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Smytheman","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Center for Global Infectious Disease Research , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T","family":"Guo","sequence":"additional","affiliation":[{"name":"Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R C","family":"van Wijk","sequence":"additional","affiliation":[{"name":"Systems Pharmacology and Pharmacy, Leiden Academic Centre for Drug Research, Leiden University ,","place":["the Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G F","family":"Hatfull","sequence":"additional","affiliation":[{"name":"University of Pittsburgh , Pittsburgh ,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A H","family":"Diacon","sequence":"additional","affiliation":[{"name":"TASK , Cape Town ,","place":["South Africa"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R N","family":"Coler","sequence":"additional","affiliation":[{"name":"Seattle Children's Research Institute, Center for Global Infectious Disease Research , Seattle, WA ,","place":["USA"]},{"name":"University of Washington School of Medicine, Department of Pediatrics , Seattle, WA ,","place":["USA"]},{"name":"University of Washington, Department of Global Health , Seattle, WA ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"van Ingen","sequence":"additional","affiliation":[{"name":"Radboud University Medical Centre, Department of Medical Microbiology, Community for Infectious Diseases & Research Institute of Medical Innovation , Nijmegen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,10,15]]},"container-title":["The Journal of Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag516\/71972734\/jiag516.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jid\/advance-article-pdf\/doi\/10.1093\/infdis\/jiag516\/71972734\/jiag516.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T15:42:33Z","timestamp":1792078953000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jid\/advance-article\/doi\/10.1093\/infdis\/jiag516\/8918423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,15]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/infdis\/jiag516","relation":{},"ISSN":["0022-1899","1537-6613"],"issn-type":[{"value":"0022-1899","type":"print"},{"value":"1537-6613","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,15]]},"article-number":"jiag516"}}