# Diverse Bacterial Anti-Phage Strategies: From the Laboratory to the Clinic

**Authors:** Yong Shao, Zhu Gao, Ying Zhang, Jianqiong Zhang

PMC · DOI: 10.3390/cimb48020191 · Current Issues in Molecular Biology · 2026-02-08

## TL;DR

This review explores how bacteria defend against phages in lab, animal, and clinical settings to improve phage therapy for antibiotic-resistant infections.

## Contribution

The paper bridges lab-based bacterial anti-phage strategies with clinical applications for phage therapy.

## Key findings

- Bacteria use diverse defense mechanisms against phages in artificial media.
- Animal and clinical studies reveal challenges in translating lab findings to real-world phage therapy.
- Understanding these interactions can improve the development of effective phage treatments.

## Abstract

Refractory infections caused by multidrug-resistant bacteria have emerged as a substantial threat to public health, prompting renewed interest in phage therapy. Bacteria and phages are ubiquitous in diverse environments, engaging in continuous interaction and co-evolution. In response to phage infection, bacteria have developed an array of defense mechanisms. Current studies on bacteria–phage interactions predominantly focus on laboratory settings using artificial media, whereas the final goal of phage therapy—to combat antibiotic-resistant bacteria—lies in its clinical application. This review describes bacterial defense strategies against phage infection in the context of laboratory-based artificial media, animal experiments and clinical cases, aiming to deepen the understanding of bacteria–phage interactions and promote the advancement of effective phage therapy for clinical applications.

## Full-text entities

- **Genes:** PilM [NCBI Gene 11372482], pilR [NCBI Gene 11372486]
- **Diseases:** Acinetobacter baumannii Infection (MESH:D000151), biliary tract infection (MESH:D001660), K. pneumoniae Infection (MESH:D011014), ventilator-associated pneumonia (MESH:D053717), Hypoxia (MESH:D000860), lung infection (MESH:D012141), injury to (MESH:D014947), sinusitis (MESH:D012852), tumor (MESH:D009369), diabetic (MESH:D003920), car accident (MESH:C566176), Klebsiella pneumoniae Infection (MESH:D007710), pancreatitis (MESH:D010195), cystic fibrosis (MESH:D003550), Bacterial infections (MESH:D001424), type IV RM (MESH:D002313), P. aeruginosa Infection (MESH:D011552), Abi (MESH:D007239), toxicity (MESH:D064420), Escherichia coli Infection (MESH:D004927)
- **Chemicals:** daunorubicin (MESH:D003630), iron (MESH:D007501), carbapenem (MESH:D015780), colanic acid (MESH:C004275), kanamycin (MESH:D007612), coelichelin (MESH:C412862), O-antigen (MESH:D019081), aminoglycosides (MESH:D000617), anthracyclines (MESH:D018943), streptomycin (MESH:D013307), hygromycin (MESH:C026273), ATP (MESH:D000255), polyamine (MESH:D011073), LPS (MESH:D008070), NAD+ (MESH:D009243), BioRender (-), potassium (MESH:D011188), cGAMP (MESH:C584311)
- **Species:** Vibrio alginolyticus (species) [taxon 663], Pseudomonas aeruginosa PA14 (strain) [taxon 652611], Bacillus subtilis (species) [taxon 1423], Escherichia coli (E. coli, species) [taxon 562], Pseudomonas aeruginosa (species) [taxon 287], Mus musculus (house mouse, species) [taxon 10090], Klebsiella pneumoniae (species) [taxon 573], Achromobacter xylosoxidans (species) [taxon 85698], Streptomyces (genus) [taxon 1883], Listeria monocytogenes (species) [taxon 1639], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Homo sapiens (human, species) [taxon 9606]
- **Mutations:** W221205R, W221205
- **Cell lines:** PAK_P1 — Mus musculus (Mouse), Hybridoma (CVCL_KT10), MBT86 — Mus musculus (Mouse), Mouse bladder transitional cell carcinoma, Cancer cell line (CVCL_4660)

## Full text

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## Figures

3 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12939059/full.md

## References

113 references — full list in the complete paper: https://tomesphere.com/paper/PMC12939059/full.md

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Source: https://tomesphere.com/paper/PMC12939059