Aqib Javaid

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...

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.

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.

Background/Objectives: Staphylococcus aureus is a well-known opportunistic pathogen that causes a wide range of infections, from cutaneous blemishes to potentially fatal systemic diseases. The increasing prevalence of antibiotic-resistant bacteria highlights the critical need for alternative therapeutic methods that target virulence factors rather than growth. Methods: The antibacterial activity of 3-fluorocatechol (3-FC) against bacterial and fungal pathogens (e.g., Candida albicans) was determined by broth microdilution to establish the lowest inhibitory concentration. The antibiofilm impact of 3-FC against S. aureus was evaluated using crystal violet staining and viable colony counts, followed by scanning electron microscopy to visualize the biofilm architecture. The methanol extraction method was used to quantify staphyloxanthin synthesis in S. aureus cells. Furthermore, in silico molecular docking was used to evaluate 3-FC binding interactions and provide mechanistic insight into its impacts on S. aureus biofilms and virulence-associated factors. Results: Although the study showed that 3-FC exhibits weak antibacterial activity against S. aureus (MIC > 2048 µg/mL), it shows effective inhibition of up to 86.5% at sub-inhibitory doses during the initial stage of biofilm formation. The CFU enumeration also confirms the significant reduction of viable cell count of S. aureus in the presence of sub-MIC of 3-FC. The SEM analysis confirms disruption of the S. aureus biofilm architecture in the presence of a sub-MIC of 3-FC. Furthermore, the eradication of mature S. aureus biofilm at a sub-MIC dose of 3-FC was 60.6%. 3-FC significantly reduced staphyloxanthin formation, a vital antioxidant pigment that contributes to bacterial pathogenicity, with a maximal suppression of 66.3% at 2048 µg/mL. Molecular docking analyses provide further insight into the molecular basis of 3-FC activity, revealing strong binding affinities with numerous S. aureus virulence regulators and enzymes, suggesting interference with quorum-sensing, adhesion, and oxidative-stress response pathways. Conclusions: Collectively, our findings indicate that 3-FC has antibiofilm and antivirulence properties against S. aureus. Furthermore, this study suggests 3-FC as a viable structural scaffold for the development of a novel anti-infective agent to treat chronic staphylococcal infections.

Foodborne pathogens remain a significant public health concern, necessitating the development of rapid, sensitive, and reliable detection methods for various food matrices. Traditional biosensors, while effective in many contexts, often face limitations related to complex sample environments, signal interpretation, and on-site usability. The integration of artificial intelligence (AI) into biosensing platforms offers a transformative approach to address these challenges. This review critically examines recent advancements in AI-assisted biosensors for detecting foodborne pathogens in various food samples, including meat, dairy products, fresh produce, and ready-to-eat foods. Emphasis is placed on the application of machine learning and deep learning to improve biosensor accuracy, reduce detection time, and automate data interpretation. AI models have demonstrated capabilities in enhancing sensitivity, minimizing false results, and enabling real-time, on-site analysis through innovative interfaces. Additionally, the review highlights the types of biosensing mechanisms employed, such as electrochemical, optical, and piezoelectric, and how AI optimizes their performance. While these developments show promising outcomes, challenges remain in terms of data quality, algorithm transparency, and regulatory acceptance. The future integration of standardized datasets, explainable AI models, and robust validation protocols will be essential to fully harness the potential of AI-enhanced biosensors for next-generation food safety monitoring.

Microbial infections are an escalating global health threat, driven by the alarming rise of antimicrobial resistance (AMR), which has made many conventional antibiotics increasingly ineffective and threatens to reverse decades of medical progress. The rapid emergence and spread of multidrug-resistant bacteria have severely limited treatment options, resulting in increased morbidity, mortality, and healthcare burden worldwide. In response to these challenges, phage therapy is regaining interest as a promising alternative. Bacteriophages, the most abundant biological entities, have remarkable specificity toward their bacterial hosts, enabling them to selectively eliminate pathogenic strains. Phage therapy presents several advantages over conventional antibiotics, which include minimal disruption to the microbiome and a slower rate of resistance development. Among the various sources of phages, the marine environment remains one of the least explored. Given their adaptation to saline conditions, high pressure, and variable nutrient levels, marine bacteriophages mostly exhibit enhanced environmental stability, broader host ranges, and distinct infection mechanisms, thus making them highly promising for therapeutic purposes. This review explores the growing therapeutic potential of marine bacteriophages by examining their ecological diversity, biological characteristics, infection dynamics, and practical applications in microbial disease control. It also deals with emerging strategies such as phage–antibiotic synergy, genetic engineering, and the use of phage-derived enzymes, alongside several challenges that must be addressed to enable clinical translation and regulatory approval. Advancing our understanding and application of marine phages presents a promising path in the global fight against AMR and the development of next-generation antimicrobial therapies.

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.