Integrated Strategies to Combat Antimicrobial Resistance: from Natural and Synthetic Products to Anti-Biofilm and Advanced Therapeutics with Innovative Targets

Antimicrobial resistance (AMR) is a growing global public health crisis, contributing to increased morbidity, mortality, and healthcare costs, as highlighted in recent reports by the World Health Organization. The inappropriate use of antibiotics—including overuse, misuse in dosage and duration, and incorrect clinical indications—has significantly accelerated this phenomenon. Importantly, AMR must be addressed within a One Health framework, recognizing the interconnected roles of human, animal, and environmental health. Despite the alarming rise in multidrug-resistant (MDR) pathogens and the increasing failure of current antimicrobial therapies, the development of new antibiotics remains limited. This critical gap necessitates the exploration of innovative and complementary strategies, including both direct antibacterial agents and resistance-modifying approaches.Among resistance mechanisms, microbial biofilms represent a major challenge. Biofilms are structured microbial communities embedded in an extracellular polymeric substance (EPS) matrix composed of exopolysaccharides, proteins, extracellular DNA, and, in some cases, outer membrane vesicles. Their composition varies depending on microbial species, environmental conditions, and developmental stage. Biofilm formation confers significant tolerance to antimicrobial agents and protection from host immune responses, contributing to chronic and persistent infections. Furthermore, polymicrobial biofilms complicate treatment strategies by requiring broad-spectrum or multi-targeted interventions. The intrinsic tolerance of biofilms is driven by multiple factors, including limited antimicrobial penetration through the EPS matrix and the presence of metabolically dormant cells. These features highlight the urgent need for innovative anti-biofilm strategies aimed at both preventing biofilm formation and eradicating established biofilms. Such strategies may involve synthetic or well-characterized natural compounds, as well as combinational and multi-target approaches capable of overcoming biofilm-associated resistance. In parallel, in silico analyses of the interaction with the target can corroborate the results.Overall, this Research Topic aims to provide a comprehensive and interdisciplinary platform integrating microbiology, medicinal chemistry, pharmacology, food chemistry, and pharmacognosy. The goal is to advance knowledge on innovative strategies to combat antimicrobial resistance, with particular attention to translational and clinically relevant applications. We invite submissions including original research articles, reviews, short communications, opinion pieces, and theoretical or hypothesis-driven contributions addressing the following sub-themes of interest:- Combination therapies (natural and synthetic compounds)- Agents targeting key resistance mechanisms: quorum sensing, efflux pumps, virulence factors, and extracellular vesicle content- Anti-biofilm strategies: prevention of biofilm formation and eradication of established biofilms- Novel molecular targets, nanosystems, and advanced drug delivery platforms- Physico-chemical methods (e.g., photodynamic therapy)- Biotechnological production, isolation, chemical characterization, and biological evaluation of natural, semi-synthetic, and synthetic compounds, including structure–activity relationships, novel mechanisms of action, and chemically modified compounds with enhanced pharmacological or pharmacokinetic profiles- Control of microbial infections (bacterial, fungal, and viral) and prevention of parasitic diseases- Food safety and preservation- Modulation of the human gut microbiota- Epidemiological and clinical investigations into therapeutic efficacy Topic editors: Simone Carradori, Rahime Şimşek, Ilaria D'Agostino, Mimoza Basholli Salihu Source: https://www.frontiersin.org/research-topics/81763/integrated-strategies-to-combat-antimicrobial-resistance-from-natural-and-synthetic-products-to-anti-biofilm-and-advanced-therapeutics-with-innovative-targets