# Precision bacterial immunotherapy: an integrated mechanistic taxonomy and translational roadmap against antimicrobial resistance

## TL;DR

This paper proposes a new approach to fighting antibiotic resistance by combining host-directed immunotherapies and precision technologies to create more effective and lasting treatments.

## Contribution

The paper introduces an integrated mechanistic taxonomy and translational roadmap for precision bacterial immunotherapy to combat antimicrobial resistance.

## Key findings

- Host-directed immunotherapies can break down biofilms and target intracellular bacterial reservoirs.
- Precision technologies like CRISPR and aptamer-guided nanoparticles enable context-sensitive targeting of resistant pathogens.
- Combining these approaches offers a translational roadmap for durable anti-infective interventions.

## Abstract

An integrated, host-directed therapeutic strategy is urgently required to outpace the accelerating threat of antimicrobial resistance (AMR), because pathogen-centred antibiotics are losing efficacy worldwide. The growing threat of antimicrobial resistance has made traditional antibiotics less and less effective, and it has also shown that our pathogen-centered treatment model has systemic flaws. Bacterial immunotherapy offers an alternative that is directed at the host. Still, its many forms, such as innate immune agonists, monoclonal antibodies, engineered cells, CRISPR-based antimicrobials, and aptamer-guided nanoplatforms, have mostly been looked at separately. We put these different approaches together in this narrative review to create a new mechanistic taxonomy that shows how they can be used together to break down biofilms, stop efflux pumps, and get rid of intracellular reservoirs. We then put each modality on a translational continuum, from bench-top proof-of-concept to late-stage trials, and find the most essential delivery, safety, and regulatory problems. Lastly, we describe a precision-first vision that uses multi-omics profiling and theranostic platforms to help with patient stratification, adaptive dosing, and real-time monitoring. This review shows a straightforward way to turn narrative insights into context-sensitive, long-lasting interventions that will work with and maybe even change the future of infectious disease medicine by co-developing immunotherapeutic strategies with advanced diagnostics and stewardship frameworks.

This diagram shows the many problems that make traditional antibiotics less effective. These include ATP-driven outer-membrane efflux pumps that actively remove antimicrobial agents, inducible enzymatic pathways that deactivate drugs when they receive signals from outside the cell, and the fact that passive delivery vehicles don’t work well enough. It also shows the convergent immunotherapeutic and precision-platform solutions that have been made to solve these problems. The lower panel shows how host-directed modalities (monoclonal antibodies and bacteriophages) use both innate and adaptive immune mechanisms to kill pathogens and break up biofilms. It also shows how precision technologies (aptamer-guided nanoparticles and CRISPR-based systems) can target specific sequences and release them at the right time in the infection environment. These complementary strategies work together to create a translational roadmap for long-lasting, context-sensitive anti-infective interventions that can get around multidrug-resistance mechanisms.Diagram illustrating antibiotic resistance barriers, including outer membrane efflux pumps, enzymes with inactive and activated forms triggered by signaling molecules, and precision platforms. Host-directed immunotherapies and precision platforms like aptamers, CRISPR, and NPS are shown, aiming for durable, context-responsive anti-infectives.

This diagram shows the many problems that make traditional antibiotics less effective. These include ATP-driven outer-membrane efflux pumps that actively remove antimicrobial agents, inducible enzymatic pathways that deactivate drugs when they receive signals from outside the cell, and the fact that passive delivery vehicles don’t work well enough. It also shows the convergent immunotherapeutic and precision-platform solutions that have been made to solve these problems. The lower panel shows how host-directed modalities (monoclonal antibodies and bacteriophages) use both innate and adaptive immune mechanisms to kill pathogens and break up biofilms. It also shows how precision technologies (aptamer-guided nanoparticles and CRISPR-based systems) can target specific sequences and release them at the right time in the infection environment. These complementary strategies work together to create a translational roadmap for long-lasting, context-sensitive anti-infective interventions that can get around multidrug-resistance mechanisms.