# Reversing Antibiotic Resistance: Strategies From Adjuvants to Innovative Therapeutics

**Authors:** Tianjiao Li, Fei Zeng, Jie Zhang, Yuangong Zhang, Wenjuan Yin

PMC · DOI: 10.1002/mbo3.70233 · 2026-02-15

## TL;DR

This paper explores new strategies to reverse antibiotic resistance by enhancing existing antibiotics and using innovative technologies like CRISPR.

## Contribution

The paper introduces molecular reversal strategies and innovative technologies to combat antibiotic resistance.

## Key findings

- Molecular reversal strategies inhibit resistance gene function and block horizontal gene transfer.
- Technologies like CRISPR-Cas and nanotechnology show promise in restoring antibiotic efficacy.

## Abstract

The escalating prevalence of antibiotic resistance has become a major threat to the effectiveness of conventional antibiotics. Meanwhile, the development of novel antibiotics faces substantial challenges, including lengthy research cycles, high costs, and the rapid emergence of bacterial tolerance, making it difficult for new drugs to keep pace with bacterial evolution. In this context, molecular reversal strategies targeting antibiotic resistance genes have emerged as a promising avenue to overcome this impasse. Among them, the use of antibiotic adjuvants, agents that enhance the efficacy of existing antibiotics by inhibiting resistance gene function, preventing their horizontal transfer or modulating host defense has gained considerable attention. Furthermore, innovative approaches such as CRISPR‐Cas gene editing, photodynamic therapy, nanotechnology, and ecological competition strategies have shown great potential in reversing antimicrobial resistance. Collectively, these strategies offer novel insights into addressing the global crisis of antibiotic resistance, paving the way for more effective clinical interventions and ensuring the sustained efficacy of current antibiotic therapies.

Molecular reversal strategies against antibiotic resistance act through three mechanisms: inhibiting resistance gene function, blocking horizontal gene transfer, and modulating host defense. Emerging technologies, such as CRISPR‐Cas gene editing, photodynamic therapy, nanotechnology, and ecological competition, further strengthen these approaches, offering innovative solutions to restore antibiotic efficacy.

## Full-text entities

- **Genes:** BCAR1 (BCAR1 scaffold protein, Cas family member) [NCBI Gene 9564] {aka CAS, CAS1, CASS1, CRKAS, P130Cas}
- **Diseases:** microbial infections (MESH:D015163), K. pneumonia (MESH:D011014), BLIs (MESH:D054179), opportunistic infections (MESH:D009894), AMR (MESH:D060467), cystic fibrosis (MESH:D003550), skin and soft tissue infections (MESH:D018461), inflammation (MESH:D007249), ARGs (MESH:D004761), MDR (MESH:D018088), bacterial infection (MESH:D001424), tuberculosis (MESH:D014376), bronchitis (MESH:D001991), A. baumannii infections (MESH:D007239), C   T (MESH:D001260), deaths (MESH:D003643), P. aeruginosa pulmonary infections (MESH:D011552)
- **Chemicals:** resveratrol (MESH:D000077185), SDS (MESH:D012967), tazobactam (MESH:D000078142), adenine (MESH:D000225), ODTAB (MESH:C518260), amoxicillin (MESH:D000658), methicillin (MESH:D008712), nitric oxide (MESH:D009569), erythromycin (MESH:D004917), niclosamide (MESH:D009534), cytosine (MESH:D003596), water (MESH:D014867), phospholipids (MESH:D010743), Avibactam (MESH:C543519), carbapenem (MESH:D015780), vancomycin (MESH:D014640), ceftazidime (MESH:D002442), Ursolic acid (MESH:C005466), coumarin (MESH:C030123), DA (MESH:C007474), meropenem (MESH:D000077731), phosphatidylglycerol (MESH:D010715), polysaccharides (MESH:D011134), MK-7655 (MESH:C568736), ethidium bromide (MESH:D004996), oxyclozanide (MESH:D010097), CIP (MESH:D002939), lincosamides (MESH:D055231), Tigecycline (MESH:D000078304), beta-lactam antibiotic (MESH:D008997), CaCO3 (MESH:D002119), EGCG (MESH:C045651), AZI (MESH:D017963), mannose (MESH:D008358), AMPs (MESH:D000089882), Aminoglycoside (MESH:D000617), beta-lactam (MESH:D047090), PLGA (MESH:D000077182), GCS (MESH:C118638), methyl orange (MESH:C100258), xylitol (MESH:D014993), CGA (MESH:D002726), bisphosphonates (MESH:D004164), oleanolic acid (MESH:D009828), eugenol (MESH:D005054), short-chain fatty acids (MESH:D005232), guanidinium (MESH:D019791), ROS (MESH:D017382), saponin (MESH:D012503), BBR (MESH:D001599), imipenem (MESH:D015378), ampicillin (MESH:D000667), ETX2514 (MESH:C000626193), Polyphenols (MESH:D059808), ofloxacin (MESH:D015242), CO2 (MESH:D002245), clavulanic acid (MESH:D019818), glycopeptides (MESH:D006020), polylactide (MESH:C033616), LPS (MESH:D008070)
- **Species:** Streptococcus pyogenes (species) [taxon 1314], Enterobacter (genus) [taxon 547], Lactobacillus acidophilus (species) [taxon 1579], aureus [taxon 46170], Mus musculus (house mouse, species) [taxon 10090], Pseudomonas aeruginosa (species) [taxon 287], Lacticaseibacillus rhamnosus (species) [taxon 47715], Klebsiella pneumoniae (species) [taxon 573], Escherichia coli (E. coli, species) [taxon 562], Bacillus subtilis (species) [taxon 1423], Enterococcus faecium (species) [taxon 1352], Streptococcus salivarius (species) [taxon 1304], Lactiplantibacillus plantarum (species) [taxon 1590], Latilactobacillus sakei (species) [taxon 1599], Acinetobacter baumannii (species) [taxon 470], Helicobacter pylori (species) [taxon 210], Staphylococcus aureus (species) [taxon 1280], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Escherichia coli Nissle 1917 (strain) [taxon 316435], Homo sapiens (human, species) [taxon 9606]

## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12906665/full.md

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Source: https://tomesphere.com/paper/PMC12906665