Biofilms are complex microbial communities encased within a self-produced extracellular matrix, which plays a critical role in chronic infections and antimicrobial resistance. These enhance pathogen survival and virulence by protecting against host immune defenses and conventional antimicrobial treatments, posing substantial challenges in clinical contexts such as device-associated infections and chronic wounds. Secondary metabolites derived from medicinal plants, such as alkaloids, tannins, flavonoids, phenolic acids, and essential oils, have gained attention as promising agents against biofilm formation, microbial virulence, and antibiotic resistance. These natural compounds not only limit microbial growth and biofilm development but also disrupt communication between bacteria, known as quorum sensing, which reduces their ability to cause disease. Through progress in nanotechnology, various nanocarriers such as lipid-based systems, polymeric nanoparticles, and metal nanoparticles have been developed to improve the solubility, stability, and cellular uptake of phytochemicals. In addition, the synergistic use of plant-based metabolites with conventional antibiotics or antifungal drugs has shown promise in tackling drug-resistant microorganisms and revitalizing existing drugs. This review comprehensively discusses the efficacy of pure secondary metabolites from medicinal plants, both as individuals and in nanoformulated forms or in combination with antimicrobial agents, as alternative strategies to control biofilm-forming pathogens. The molecular mechanisms underlying their antibiofilm and antivirulence activities are discussed in detail. Lastly, the current pitfalls, limitations, and emerging directions in translating these natural compounds into clinical applications are critically evaluated.

Prophages are bacteriophage genomes that are part of bacterial chromosomes. They are not just dormant passengers; they actively shape pathogen biology. For example, in skin-infecting pathogens such as Staphylococcus aureus, Streptococcus pyogenes, and Pseudomonas aeruginosa, prophages carry important virulence factors, cytotoxins, superantigens, immune evasion clusters, and epigenetic regulators that directly affect the course of skin and soft tissue infections. This same prophage biology provides a therapeutic strategy: prophage-derived molecules, including endolysins, holins, spanins, and polysaccharide depolymerases, demonstrate potent antimicrobial and antibiofilm activity against drug-resistant skin pathogens, with several candidates now in clinical development. Engineered chimeric lysins, CRISPR-encoded prophage delivery systems, and the systematic mining of the skin microbiome phageome collectively enhance the translational potential of this biology. This review integrates mechanistic insights into prophage-mediated virulence. It assesses the translational landscape of prophage-derived therapeutics, delineating the conceptual and clinical frontiers that characterize the forthcoming chapter in this domain.

Vibriosis causes substantial losses in marine and brackish-water aquaculture, while increasing antimicrobial resistance limits the effectiveness of conventional antibiotic treatment. Biofilm formation and quorum-sensing-controlled virulence further contribute to the persistence of pathogenic Vibrio species. Prophages integrated into Vibrio genomes encode proteins and regulatory elements that may provide alternative approaches for controlling these pathogens. This review evaluates endolysins, polysaccharide depolymerases, nucleases, holins, spanins, tailocins, regulatory proteins, and small RNAs associated with prophages and related phages. The available evidence was classified according to molecular origin to distinguish validated prophage-derived molecules from those obtained from temperate or lytic phages and from molecules characterized in non-Vibrio bacteria. Endolysins and depolymerases can disrupt bacterial cells and biofilm matrices, whereas prophage regulatory elements may influence quorum sensing, adhesion, motility, toxin production, and secretion systems. However, the evidence directly supporting prophage-derived anti-Vibrio agents remains limited. Most experimentally demonstrated activity has been reported for endolysins and one validated depolymerase, and many of these molecules originated from lytic rather than temperate phages. No direct Vibrio-specific evidence is currently available for phage-derived nucleases, holins, spanins, or tailocins as isolated control agents. Prophage genomes nevertheless provide an extensive source of regulatory and antimicrobial candidates for further investigation. Progress toward aquaculture application will require experimental validation, effective delivery methods, safety assessment, scalable production, and clear regulatory standards.

Staphylococcus pseudintermedius is a common opportunistic pathogen in companion animals and a leading cause of skin and soft tissue infections (SSTIs). Despite its clinical relevance, the genomic determinants underlying pathogenicity and the transition from commensal carriage to invasive infection remain poorly understood. This study aimed to identify the genomic determinants of SSTI pathogenic potential in S. pseudintermedius and to determine whether pathogenicity is driven by single, major-effect virulence genes or by polygenic genome-wide genetic architecture. Using accessory gene-based and unitig-based genome-wide association studies (GWASs), employing a linear mixed model, across a genetically diverse collection of S. pseudintermedius isolates spanning multiple phylogenetic clades, we found that disease and carriage isolates showed no phylogenetic clustering. SSTI pathogenicity exhibited high narrow-sense heritability. Surface-associated LPXTG-anchored proteins, particularly spsF, harbored the strongest associations, with additional signals in iron metabolism (narH, sufB) and oxidative stress tolerance (ahpC). Random Forest classification validated GWAS signals. SSTI pathogenicity in S. pseudintermedius reflects a polygenic architecture driven by cumulative variation across surface-associated, metabolic, and stress-response loci, shifting focus from single virulence genes to genome-wide genetic variation.

1. The oral cavity is not a static ecosystem; rather, it is a dynamic, ever-changing ecological niche in which hundreds of microorganisms compete for attachment sites, nutrients, and immunomodulato...