Antibiotic resistance is one of the most urgent public health threats of the 21st century, projected to cause 10 million deaths per year by 2050 if left unchecked. The pipeline of new antibiotics has thinned dramatically, while multidrug-resistant (MDR) and extensively drug-resistant (XDR) pathogens continue to emerge across hospital and community settings. Conventional drug discovery has struggled to keep pace, prompting a search for fundamentally different therapeutic paradigms.

Three fields are converging to fill this gap. Nanotechnology offers carriers and intrinsically antimicrobial materials that bypass classical resistance mechanisms. Plant-derived bioactive compounds — long used in traditional medicine — provide a vast, underexplored chemical space with novel modes of action. Artificial intelligence and machine learning now make it possible to mine this space at scale, predict activity, and optimise delivery systems that were previously beyond reach.

This Research Topic brings together advances at the interface of nanotechnology, phytochemistry, and AI to accelerate the development and translation of next-generation antimicrobial therapies. The central problem is twofold: existing antibiotics are losing efficacy faster than replacements can be developed, and many promising natural compounds suffer from poor solubility, instability, or low bioavailability that prevents clinical use.

We invite work that addresses these challenges through integrated therapeutic strategies — screening of phytochemical libraries against resistant pathogens, design of nanocarriers that protect and deliver bioactive compounds to infection sites, and machine learning models that predict synergy between plant metabolites and existing antibiotics. The unifying thread across all contributions is mechanistic clarity: how does the approach actively circumvent, disable, or reverse a defined resistance mechanism? Recent advances in graph neural networks, green-synthesized metallic nanoparticles, lipid and polymeric nanocarriers, and biofilm-targeted delivery systems confirm that this convergence is no longer aspirational. By gathering this work in one place, the Topic aims to map the current state of the art, surface translational bottlenecks, and outline a roadmap for moving these therapies from bench to bedside.

We welcome contributions across the following themes:

- Phytochemicals and plant extracts with activity against MDR/XDR pathogens
- Green and biogenic synthesis of antimicrobial nanoparticles
- Nano-encapsulation and targeted delivery of phytochemicals or antibiotics where the formulation confers a resistance-overcoming advantage (e.g. efflux pump evasion, membrane penetration, biofilm penetration)
- Biofilm disruption and quorum-sensing inhibition by nano-phytochemical formulations
-Combination strategies: phytochemicals as antibiotic adjuvants or resistance-breakers, with mechanistic evidence of synergy or re-sensitisation
- In vivo, ex vivo, and clinical evaluation of nano-phytochemical therapeutics
- Toxicity, safety, regulatory, and scale-up considerations

Are you interested in contributing a manuscript to this Research Topic?

Next-Generation Strategies Against Antibiotic Resistance: From Phytochemicals to Nanotechnology