Emerging anti-infective strategies based on host regulation and host–pathogen interactions

Antimicrobial resistance continues to worsen, posing a major challenge to the prevention and management of infections caused by multidrug-resistant bacteria. Although conventional antibiotics, antimicrobial nanomaterials, and phage therapy have expanded the available antimicrobial options, their application remains constrained by selective pressure for resistance, biosafety concerns, narrow host range, and incomplete clinical translation. Strategies that target the host or the host–pathogen interface have therefore attracted increasing attention. Rather than relying exclusively on direct bacterial killing, these approaches seek to improve pathogen clearance by strengthening host defenses, calibrating harmful inflammation, restoring microbial homeostasis, attenuating bacterial virulence, or inducing protective immunity. This review synthesizes current evidence on host-directed therapy, dual pathogen–host targeting, immunomodulatory polysaccharides, and next-generation bacterial vaccines, with emphasis on their mechanisms, translational potential, and unresolved challenges. Collectively, these approaches may support the development of more sustainable interventions against emerging and multidrug-resistant bacterial infections.