Design of Fmoc-Phenylalanine Nanofibrillar Hydrogel and Mechanistic Studies of Its Antimicrobial Action against Both Gram-Positive and Gram-Negative Bacteria.

In pursuit of efficient antimicrobial agents, biomaterials such as hydrogels have drawn a considerable amount of attention due to their numerous advantages such as a high degree of hydration, biocompatibility, stability, and direct application at an infectious site. Particularly, biomaterials such as hydrogels based on Fmoc-protected peptides and amino acids have proven to be immensely advantageous. Such biomaterials can undergo gelation by simple pH modulation and can be used for various biological applications. Keeping this in mind, in this work, we reported the synthesis of Fmoc-phenylalanine (Fmoc-F)-based hydrogels using trisodium citrate as a pH modulator and compared them with the previously reported pH modulator glucono-δ-lactone. The gels were compared using various characterization techniques such as rheometry, field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), small angle X-ray scattering (SAXS), FT-IR, thioflavin T (ThT) binding assay, and zeta potential studies. These studies highlighted the role of pH modulators in affecting various parameters such as the ability to alter the zeta potential of the nanofibrils, improve their bactericidal action, reduce the amyloidic characters, shift the lattice packing from amorphous to crystalline, and introduce fluorescence and thermoreversibility. Interestingly, this is the first report where the Fmoc-F-based hydrogel has been shown to be effective against Gram-negative bacteria along with Gram-positive bacteria as well. Additionally, the mechanism of antimicrobial action was investigated using docking and antioxidant studies.

Targeting bacterial biofilms using vancomycin and multivalent cell-penetrating peptide labeled quantum dots.

Bacterial biofilms are highly resilient microbial musters that are difficult to eradicate, driving the development of novel therapeutic strategies. The current study aims to investigate the therapeutic efficacy of cell-penetrating peptide-based targeted delivery of vancomycin functionalized quantum dots in eradicating biofilm formation in gram-positive and gram-negative bacterial strains. The conjugate was characterized using fluorimetry, UV-visible spectroscopy, gel electrophoresis, and zeta potential. The conjugate was then tested for antimicrobial and antibiofilm activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, and it demonstrated excellent antimicrobial as well as antibiofilm activity against all the tested strains. The findings indicated that the conjugate was capable of overcoming bacterial resistance of bacteria in addition to the eradication of biofilms at effective concentrations.