This report illustrates a strategy for designing a nanoconjugate derived vector that efficiently delivers antimicrobial drug directly into bacterial cells. The nanoconjugate comprises of negatively charged CDTe@CdS quantum dots (QDs) with its surface functionalized using cationic BP-100 (KKLFKKILKYL-amide), a known cell-penetrating peptide (CPP), via electrostatic approach. The interactions between QD and CPP in QD-functionalized CPPs (QD−CPP) have been well analyzed using fluorescence spectroscopy, gel electrophoresis, and ζ-potential analysis. The QD−CPP conjugate was internalized into Gram negative (Escherichia coli) as well as Gram positive (Staphylococcus aureus) bacterial strains with confocal studies exhibiting a strong signal in tested microorganisms. Further, to check the applicability of QD−CPP conjugate as a delivery vector for generating an effective therapeutics, ampicillin molecules were conjugated on QD−CPP surface to generate QD−CPP−Amp conjugate. The CPP and drug molecules on the surface of QDs were well quantified using high-performance liquid chromatography (HPLC) data. It was observed that the internalization and bacterial debilitation of the QD−CPP−Amp conjugate is 2-to 4-fold effective as compared to that of bare ampicillin. The morphological changes to the bacterial cells upon the treatment with QD−CPP−Amp conjugates were noted with no cytotoxic effect on tested mammalian cell lines. The results inferred that the proposed QD−CPP vector provides a targeted and proficient approach for cellular internalization of cargo (drug) in bacterial cells with effective tracking through florescent QDs.
Novel antifungal peptides are described with some peptides exhibiting selective activity againstC. neoformans. Cytotoxicity and mechanistic studies reveal their applicability as effective antimicrobials with less susceptibility to drug resistance.
Two series of short cationic antimicrobial peptides (CAMPs) in which modification of the imidazole ring of histidine by bulkier alkyl substituents was done using regiospecific and radical‐mediated alkylation. The synthesized CAMPs were evaluated for their antibacterial efficacy using different bacterial strains. In particular, CAMP 11 i was found to be most active against L. monocytogenes and other CAMPs such as 10 e and 11 g exhibited moderate activity against S. aureus.The most active compounds were tested against Hek‐293 and HeLa cells with active CAMPs 11 i and 11 g with calculation of selectivity index against the L. monocytogenesand S. aureus, respectively as compared to mammalian cells. The SEM studies were also performed which confirmed the disruption of cell wall of treated bacteria using CAMP 11 i at its MIC concentration. The selectivity of active peptides towards bacterial cells in comparison to mammalian cells was checked using tryptophan quenching studies on small unilamellar vesicles. The results were found to be perfectly in corroboration with the differences between bacterial and mammalian cell membrane composition, thereby, indicating that these peptides kill the bacterial cells via conjugation with the cell membrane. Synergy studies of CAMPs in combination with known clinical antibacterial drugs against L. monocytogenes further displayed enhanced antibacterial efficacy.
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