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1. Metabolites derived from bacterial isolates of the human skin microbiome inhibit Staphylococcus aureus biofilm formation

   https://doi.org/10.1128/spectrum.01306-25  

   Le, Viet Hoang; King, Tetyana; Wuerzberger, Breanna; Bauer, Olivia R; Carver, Megan N; Chan, Tiffany S; Henson, Annabeth L; Hubbard, Grace K; Kopadze, Tamar; Patterson, Claire F; et al (September 2025, Microbiology Spectrum)

   Claesen, Jan (Ed.)

   ABSTRACT The human skin microbiome is a diverse ecosystem that can help prevent infections by producing biomolecules and peptides that inhibit growth and virulence of bacterial pathogens.Staphylococcus aureusis a major human pathogen responsible for diseases that range from acute skin and soft tissue infections to life-threatening septicemia. Its ability to form biofilms is a key virulence factor contributing to its success as a pathogen as well as to its increased antimicrobial resistance. Here, we investigated the ability of bacterial skin commensals to produce molecules that inhibitS. aureusbiofilm formation. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) identified 77 human skin microbiome bacterial isolates fromStaphylococcusandBacillusgenera. Metabolites from cell-free concentrated media (CFCM) from 26 representative isolates were evaluated for their ability to inhibit biofilm formation by both methicillin-resistant (MRSA) and methicillin-sensitive (MSSA)S. aureusstrains. CFCM, derived from most of the isolates, inhibited biofilm formation to varying extents but did not inhibit planktonic growth ofS. aureus. Size fractionation of the CFCM of threeS.epidermidisisolates indicated that they produce different bioactive molecules. Cluster analysis, based on either MALDI-TOF mass spectra or whole-genome sequencing draft genomes, did not show clear clusters associated with levels of biofilm inhibition amongS. epidermidisstrains. Finally, similar biosynthetic gene clusters were detected in allS. epidermidisstrains analyzed. These findings indicate that several bacterial constituents of the human skin microbiome display antibiofilmin vitroactivity, warranting further investigation on their potential as novel therapeutic agents. IMPORTANCEThe skin is constantly exposed to the environment and consequently to numerous pathogens. The bacterial community that colonizes healthy skin is thought to play an important role in protecting us against infections.S. aureusis a leading cause of death worldwide and is frequently involved in several types of infections, including skin and soft tissue infections. Its ability to adhere to surfaces and produce biofilms is considered an important virulence factor. Here, we analyzed the activity of different species of bacteria isolated from healthy skin onS. aureusbiofilm formation. We found that some species ofStaphylococcusandBacilluscan reduceS. aureusbiofilm formation, although a generally lower level of inhibitory activity was observed compared toS. epidermidisisolates. AmongS. epidermidisisolates, strength of activity was dependent on the strain. Our data highlight the importance of mining the skin microbiome for isolates that could help combat skin pathogens. 

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2. Role of Staphylococcus aureus’s Buoyant Density in the Development of Biofilm Associated Antibiotic Susceptibility

   https://doi.org/10.3390/microorganisms12040759  

   Kispert, Sarah; Liguori, Madison; Velikaneye, Cody; Qiu, Chong; Wang, Shue; Zhang, Nan; Gu, Huan (April 2024, Microorganisms)

   Biofilms are clusters of microorganisms that form at various interfaces, including those between air and liquid or liquid and solid. Due to their roles in enhancing wastewater treatment processes, and their unfortunate propensity to cause persistent human infections through lowering antibiotic susceptibility, understanding and managing bacterial biofilms is of paramount importance. A pivotal stage in biofilm development is the initial bacterial attachment to these interfaces. However, the determinants of bacterial cell choice in colonizing an interface first and heterogeneity in bacterial adhesion remain elusive. Our research has unveiled variations in the buoyant density of free-swimming Staphylococcus aureus cells, irrespective of their growth phase. Cells with a low cell buoyant density, characterized by fewer cell contents, exhibited lower susceptibility to antibiotic treatments (100 μg/mL vancomycin) and favored biofilm formation at air–liquid interfaces. In contrast, cells with higher cell buoyant density, which have richer cell contents, were more vulnerable to antibiotics and predominantly formed biofilms on liquid–solid interfaces when contained upright. Cells with low cell buoyant density were not able to revert to a more antibiotic sensitive and high cell buoyant density phenotype. In essence, S. aureus cells with higher cell buoyant density may be more inclined to adhere to upright substrates. 

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3. Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents

   https://doi.org/10.3390/antibiotics11070939  

   Raj KC, Hansa; Gilmore, David F.; Alam, Mohammad A. (July 2022, Antibiotics)

   From a library of compounds, 11 hit antibacterial agents have been identified as potent anti-Gram-positive bacterial agents. These pyrazole derivatives are active against two groups of pathogens, staphylococci and enterococci, with minimum inhibitory concentration (MIC) values as low as 0.78 μg/mL. These potent compounds showed bactericidal action, and some were effective at inhibiting and eradicating Staphylococcus aureus and Enterococcus faecalis biofilms. Real-time biofilm inhibition by the potent compounds was studied, by using Bioscreen C. These lead compounds were also very potent against S. aureus persisters as compared to controls, gentamycin and vancomycin. In multiple passage studies, bacteria developed little resistance to these compounds (no more than 2 × MIC). The plausible mode of action of the lead compounds is the permeabilization of the cell membrane determined by flow cytometry and protein leakage assays. With the detailed antimicrobial studies, both in planktonic and biofilm contexts, some of these potent compounds have the potential for further antimicrobial drug development. 

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4. Inhibition of biofilm formation induced by functional graphenic materials impregnated in Nile tilapia (Oreochromis niloticus) skin

   https://doi.org/10.1016/j.apsusc.2021.151768  

   Antonio_Gomes_da_Silva, Fernando; Eckhart, Karoline E; Matiuzzi_da_Costa, Mateus; Sydlik, Stefanie A; Pequeno_de_Oliveira, Helinando (February 2022, Applied Surface Science)

   Frederiksberg, Dr_Henrik_Rudolph (Ed.)

   Wound dressings based on natural materials, such as fish skin, represent an important strategy for the treatment of burns. Despite their utility, contamination of these natural materials with bacteria (planktonic and biofilm forms) introduces significant risks to patients under treatment. This disadvantage can be overcome by modifying the material’s surface to prevent bacterial deposition through chemical or physical interactions. In this work, functional graphenic materials (FGM) with tunable surface charges were incorporated into tilapia (Oreochromis niloticus) fish skin as a part of a strategy to control the biofilm adhesion on surfaces. The antibiofilm activity was evaluated against S. aureus and K. pneumoniae due to the biofilm-forming properties of these bacterial strains. FGM-modified tilapia skin samples possess a strong capacity to reduce biofilm formation on the tilapia fish skin with a higher antibiofilm activity against Gram-positive bacteria, compared to Gram-negative bacteria. Negatively charged FGMs were more effective than positively charged FGMs in preventing biofilm formation on the impregnated tilapia skin xenografts: negatively charged Claisen graphene achieved an 88.8% reduction in biofilm formation on the tilapia skin. Overall, this study demonstrates the utility of FGM-impregnated tilapia skins as a treatment for burn wounds due to their ability to modulate bacterial adhesion. 

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5. Methicillin-Resistant Staphylococcus aureus (MRSA): Antibiotic-Resistance and the Biofilm Phenotype

   https://doi.org/10.1039/C9MD00044E  

   Craft, Kelly M.; Nguyen, Johny; Berg, Lawrence; Townsend, Steven (January 2019, MedChemComm)

   Staphylococcus aureus (S. aureus) is an asymptomatic colonizer of 30% of all human beings. While generally benign, antibiotic resistance contributes to the success of S. aureus as a human pathogen. Resistance is rapidly evolved through a wide portfolio of mechanisms including horizontal gene transfer and chromosomal mutation. In addition to traditional resistance mechanisms, a special feature of S. aureus pathogenesis is its ability to survive on both biotic and abiotic surfaces in the biofilm state. Due to this characteristic, S. aureus is a leading cause of human infection. Methicillin-resistant S. aureus (MRSA) in particular has emerged as a widespread cause of both community- and hospital-acquired infections. Currently, MRSA is responsible for 10-fold more infections than all multi-drug resistant (MDR) Gram-negative pathogens combined. Recently, MRSA was classified by the World Health Organization (WHO) as one of twelve priority pathogens that threaten human health. In this targeted mini-review, we discuss MRSA biofilm production, the relationship of biofilm production to antibiotic resistance, and front-line techniques to defeat the biofilm-resistance system. 

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