REVIEW article
Front. Microbiol.
Sec. Antimicrobials, Resistance and Chemotherapy
This article is part of the Research TopicUtilizing CRISPR-Cas Systems to Combat Antibacterial ResistanceView all articles
Next-Generation Bacteriophage Therapeutic Systems: CRISPR-Based Engineering, Near-Infrared Bioimaging, and Precision Strategies for Treating Multidrug-Resistant and Extensively Drug-Resistant Bacterial Infections
Provisionally accepted
- 1Szechenyi Istvan Egyetem, Győr, Hungary
- 2Korea University, Seongbuk-gu, Republic of Korea
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
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 blaNDM, mecA, and mcr-1. 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 in vivo 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 Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, Burkholderia cepacia, and Mycobacterium abscessus. 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.
Keywords: Bacteriophage therapy, biofilm disruption, CRISPR-engineered bacteriophages, Extensively drug-resistant bacteria, Jumbo phages, Multidrug-resistant bacteria, near-infrared bioimaging, phage pharmacokinetics
Received: 18 Nov 2025; Accepted: 12 Jan 2026.
Copyright: © 2026 Saeed and PIRACHA. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Umar Saeed
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.