{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T20:20:36Z","timestamp":1792182036715,"version":"4.4.0"},"reference-count":130,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p>\n                    The rapid rise of multidrug-resistant and extensively drug-resistant bacterial infections has renewed interest in bacteriophages as adaptable, targeted antimicrobials. Recent advances in phage engineering, including CRISPR-based approaches, now make it possible to refine host range, strengthen lytic performance, and deliver genetic payloads that target clinically important resistance determinants such as\n                    <jats:italic>blaNDM<\/jats:italic>\n                    ,\n                    <jats:italic>mecA<\/jats:italic>\n                    , and\n                    <jats:italic>mcr-1<\/jats:italic>\n                    . In parallel, jumbo phages with large genomes often encode additional functions that support replication and biofilm disruption, offering practical advantages in densely structured infections where antibiotics perform poorly. A second limitation in phage translation has been measurement: in most settings, dosing and treatment duration remain guided by indirect endpoints rather than real-time information on distribution and activity. Near-infrared bioimaging addresses this gap by enabling noninvasive tracking of infection burden and phage kinetics\n                    <jats:italic>in vivo<\/jats:italic>\n                    through bacteriophytochrome-derived reporters, including iRFPs, miRFPs, and PAiRFPs. In this review, we bring these developments together and discuss how CRISPR-enabled phage engineering, jumbo-phage biology, and near-infrared readouts can be integrated into a precision framework that is measurable, adaptable, and clinically interpretable. We examine evidence across major drug-resistant pathogens, including\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    ,\n                    <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    ,\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    , vancomycin-resistant enterococci,\n                    <jats:italic>Burkholderia cepacia<\/jats:italic>\n                    , and\n                    <jats:italic>Mycobacterium abscessus<\/jats:italic>\n                    . We also summarize practical constraints that remain central to clinical translation, manufacturing quality, host immune neutralization, and regulatory variability, and outline a realistic development pathway in which engineered phages and companion diagnostics progress from animal models to carefully defined clinical indications. Together, these advances support a shift from empirical phage use toward a more standardized, data-driven approach to treating drug-resistant infections.\n                  <\/jats:p>","DOI":"10.3389\/fmicb.2026.1748742","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T08:47:53Z","timestamp":1775033273000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Next-generation bacteriophage therapeutic systems: CRISPR-based engineering, near-infrared bioimaging, and precision strategies for treating multidrug-resistant and extensively drug-resistant bacterial infections"],"prefix":"10.3389","volume":"17","author":[{"given":"Zahra Zahid","family":"Piracha","sequence":"first","affiliation":[{"name":"Sz\u00e9chenyi Istv\u00e1n University","place":["Gy\u0151r, Hungary"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umar","family":"Saeed","sequence":"additional","affiliation":[{"name":"University College, Korea University","place":["Seoul, Republic of Korea"]},{"name":"Institute of Graduate Studies and Research, Cyprus International University","place":["Nicosia, Cyprus"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"66","DOI":"10.4161\/bact.1.2.15845","article-title":"Phage treatment of human infections","volume":"1","author":"Abedon","year":"2011","journal-title":"Bacteriophage"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1038\/s41586-020-2279-8","article-title":"Massively multiplexed nucleic acid detection with Cas13","volume":"582","author":"Ackerman","year":"2020","journal-title":"Nature"},{"key":"ref3","volume-title":"Real-world registry outcomes and PhageBank 2020\u20132025","year":""},{"key":"ref8007","article-title":"FDA clears first clinical study for a Polymicrobial phage library-based treatment for antibiotic-resistant infections [internet]","year":"2020","journal-title":"Business Wire"},{"key":"ref4","article-title":"Phage cocktail against ST258 K. pneumoniae","volume":"10","author":"Aleshkin","year":"2021","journal-title":"Antibiotics (Basel)"},{"key":"ref9007","doi-asserted-by":"publisher","first-page":"199426","DOI":"10.1016\/j.virusres.2024.199426","article-title":"A diverse set of Enterococcus-infecting phage provides insight into phage host-range determinants","volume":"347","author":"Alrafaie","year":"2024","journal-title":"Virus Res."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1038\/s41586-020-2007-4","article-title":"Clades of huge phages from across earth\u2019s ecosystems","volume":"578","author":"Al-Shayeb","year":"2020","journal-title":"Nature"},{"key":"ref8001","volume-title":"Armata pharmaceuticals announces clearance of investigational new drug application to initiate phase 2 clinical trial of AP-PA02 in non-cystic fibrosis bronchiectasis [internet]","year":""},{"key":"ref8002","volume-title":"Pseudomonas aeruginosa phage product candidates (AP-PA02) [internet]","year":""},{"key":"ref7","first-page":"3106","article-title":"Early clinical experience of bacteriophage therapy in 20 patients with multidrug-resistant bacterial infections","volume":"71","author":"Aslam","year":"2020","journal-title":"Clin. 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