Objectives: The goal of this study is to develop a novel drug delivery platform for the pH-responsive delivery of biofilm inhibitors as a potential avenue to prevent and treat dental caries.
Methods: Biofilm and growth inhibition assays were performed in polystyrene microtiter 96-well plates. Docking analysis was performed using the reported GtfB + HA5 co-crystal structure (PDB code: 8fg8) in SeeSAR 13.
We designed and synthesized analogues of a previously identified biofilm inhibitor to improve solubility, retain inhibitory activities, and to facilitate encapsulation into pH-responsive hydrogel microparticles. The optimized lead compound showed improved solubility of 120.09 μg/mL, inhibited biofilm with an IC value of 6.
View Article and Find Full Text PDFresides in the oral polymicrobial biofilm and is a major contributor to the development of dental caries. Interestingly, high salivary nitrite concentrations have been associated with a decreased prevalence of dental caries. Moreover, the combination of hydrogen peroxide-producing oral commensal streptococci and nitrite has been shown to mediate the generation of reactive nitrogen species, which have antimicrobial activity.
View Article and Find Full Text PDFFrancisella tularensis is an infectious, gram-negative, intracellular microorganism, and the cause of tularemia. Invasion of host cells by intracellular pathogens like Francisella is initiated by their interaction with different host cell membrane receptors and the rapid phosphorylation of different downstream signaling molecules. PI3K and Syk have been shown to be involved in F.
View Article and Find Full Text PDFAntimicrob Agents Chemother
February 2013
We and others recently identified copper resistance as important for virulence of Mycobacterium tuberculosis. Here, we introduce a high-throughput screening assay for agents that induce a copper hypersensitivity phenotype in M. tuberculosis and demonstrate that such copper-boosting compounds are effective against replicating and nonreplicating M.
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