Editorial: Innovative antibiofilm strategies: advancing the management of microbial biofilm infections

homeostasis and interspecies molecular communication at the center of biofilm biology, highlighting targets that are neither conventional resistance genes nor essential growth determinants, but modulators of community architecture and virulence expression. Environmental control represents a second organizing theme. An et al. examine Pseudomonas aeruginosa from pulmonary infections and show that iron availability simultaneously enhances growth, adhesion, and biofilm formation while attenuating acute virulence phenotypes. This finding highlights an important principle: microbial persistence can be sustained by adaptive states that enhance colonization, tissue residence, and immune evasion while attenuating acute virulence. Similarly, Afsharnia et al. use transcriptomics to show that glucosamine, but not its acetylated derivative N-acetylglucosamine, suppresses S. aureus biofilm formation through broad metabolic rewiring, including effects on adhesion genes, arginine biosynthesis, the tricarboxylic acid cycle, urea metabolism, and pH homeostasis. These findings suggest that metabolism actively supports biofilm formation and persistence. Targeting key metabolic pathways may therefore weaken biofilm structure and enhance the effectiveness of biofilm control strategies. A third focus of this Research Topic concerns the development of experimental models that more accurately recapitulate biofilm-associated infections as they occur in clinical settings and on medical devices. Reese et al. introduce a modular dual-loop chemostat for multispecies biofilms on implantrelevant surfaces under independently adjustable nutrient and flow conditions. By decoupling cultivation from hydrodynamic exposure, the system captures a neglected determinant of biofilm phenotype: shear stress. Their findings, including flow-dependent shifts in biomass, robustness, matrix content, and species distribution on titanium surfaces, underscore the limitations of static monospecies assays and provide a platform for testing antimicrobial coatings and implant designs under more realistic physical constraints. Such technologies are essential if the antibiofilm field is to improve its predictive power. That translational gap is also addressed by Verheul et al., who evaluate whether the activity of phageantibiotic combinations against planktonic S. aureus can reliably predict their activity against mature biofilms on metal implant mimics. Their data have clear translational relevance, showing that planktonic screening was effective in identifying antagonistic interactions, but had limited ability to predict synergistic effects following repeated treatment of mature biofilms. Thus, while rapid planktonic testing may help exclude harmful combinations, biofilm-specific models remain necessary to identify truly effective regimens. This distinction is particularly relevant as bacteriophage gains renewed clinical interest and combination design becomes increasingly empirical (Palma and Qi, 2024;Gallina et al., 2026). Several contributions explore antibiofilm approaches derived from natural, host-associated, or sustainable sources. For instance, Ma et al. show that stevioside, a natural sweetener, reduces Streptococcus mutans biofilm formation, acid production, bacterial viability, extracellular polysaccharide synthesis, and the expression of virulence-related genes, positioning it as an anticariogenic strategy for oral health. Sateriale et al. demonstrate that polyphenol-rich pomegranate peel extract from agri-food waste exerts antifungal activity against emerging Candida pathogens, interfering with membrane permeability, germ-tube formation, adhesion, and established biofilms. Rehman et al. add a host-derived dimension by showing that human urinary extracellular vesicle preparations inhibit biofilm formation by uropathogenic Escherichia coli, P. aeruginosa, and Klebsiella pneumoniae at physiologically relevant concentrations, without merely inhibiting planktonic growth. These studies converge on a key point: antibiofilm activity may arise from agents that attenuate virulence, adhesion, or community formation rather than from direct microbicidal pressure alone. The review by Nakazwe et al. places these strategies within the broader framework of "resistance breakers", agents designed to disable the mechanisms that allow biofilms to tolerate antimicrobial exposure. By targeting the matrix, efflux systems, enzymatic defenses, membrane permeability, quorum sensing, or biofilm metabolism, these approaches seek to restore the activity of existing antimicrobials by weakening the protective biofilm state. This concept is particularly relevant in light of the persistent limitations of the antibacterial pipeline and the biofilm capacity to compromise the effectiveness of available therapies (Ciofu et al., 2022;World Health Organization, 2024). Engineered materials and nanotechnologies represent another translational frontier. López-Lisbona et al. focus on tracheobronchial stents, a clinically important surface where bacterial colonization can complicate airway management. Their study identifies P. aeruginosa and S. aureus as frequent colonizers after stent placement and shows that silver-coated silicone markedly reduces the viability of clinical isolates on silicone surfaces. Tan et al. develop a redox-responsive ginsenoside-copper nanoagent that remains stable under physiological conditions but releases active components and generates reactive oxygen species in reducing environments, thereby exerting antibacterial and biofilm-disruptive effects against both Gram-positive and Gram-negative bacteria, with favorable in vitro biocompatibility. Collectively, these studies exemplify the ongoing transition from passive biomaterials to active anti-infective surfaces and responsive nanosystems (Balaure and Grumezescu, 2020;Su et al., 2025). Host-directed and biophysical strategies further broaden the therapeutic landscape of antibiofilm research. Wilbanks et al. demonstrate that biofilm collapse induced by a DNABII-targeted monoclonal antibody releases nontypeable Haemophilus influenzae cells in a state more readily recognized by neutrophils, thereby promoting engulfment, NETosis, and immune-cell migration. These findings support the emerging concept that disrupting the matrix can shift bacteria from a protected immune-evasive state to one that is more vulnerable to host clearance (Fleming and Rumbaugh, 2018;Ciofu et al., 2022). Bhasme et al. review how electrical and redox cues shape wound repair and microbial behavior, influencing epithelial regeneration, immune responses, bacterial energetics, quorum sensing, and matrix organization. Together, these studies suggest that biofilm control is a system-level challenge requiring coordinated modulation of microbial, host, and environmental determinants that sustain persistence. Across the studies of the Research Topic, a subtle but important methodological message emerges. Biofilm research must now move beyond the simple question of whether an intervention reduces biomass and instead focus on the biological transition it induces within the biofilm ecosystem. Does it prevent initial attachment, weaken the matrix, force dispersal, sensitize persister-like cells, alter metabolic heterogeneity, restore immune access or reduce the risk of recurrence? Does it act similarly across strains, species and surfaces, or does it depend on local ecology? These questions matter because a reduction in crystal-violet staining, a decrease in colony counts, a shift in matrix composition and an increase in immune clearance are not interchangeable outcomes. The next generation of antibiofilm research will therefore require integrated readouts that connect structure, viability, function, host response and clinical feasibility. Taken together, the contributions in this Research Topic reveal four priorities for the next phase of antibiofilm research. First, therapeutic discovery must target biofilm-specific physiology, including second-messenger signaling, protein homeostasis, matrix biosynthesis, metabolism and environmental sensing. Second, models must become more clinically faithful by incorporating multispecies communities, shear forces, implant surfaces, host effectors, and repeated treatment schedules. Third, antibiofilm strategies should be evaluated not only for biomass reduction or killing, but also for their ability to alter virulence, dispersal state, immune susceptibility, recurrence potential, and compatibility with existing antimicrobials. Fourth, translation will require integration: phages with antibiotics, coatings with diagnostics, natural products with mechanistic validation, host-derived factors with immunology, and electroceuticals with real-time sensing. The field is entering a more ambitious stage. Biofilms are no longer viewed solely as barriers to drug penetration; they are ecosystems with regulatory logic, material properties, metabolic dependencies, and host interfaces. The clinical burden of biofilm-associated infection remains significant, but the conceptual and technological toolkit is expanding rapidly. By integrating mechanistic microbiology, biomaterials science, nanotechnology, natural-product research, host-pathogen biology, and bioelectronic medicine, this Research Topic captures the diversity of strategies now required to advance from in vitro antibiofilm activity to durable infection control in patients.