Based on the determination on the kinase specificity of current inhibitors

Based on our dextran-coated magnetic nanosensors�� ability to sense carbohydrate utilization due to microbial metabolism, we examined if these nanosensors can be used for the identification of antimicrobial susceptibility and determination of an antibiotic��s minimum inhibitory concentration. As MIC predicts the success of a particular antibiotic and is an important clinical parameter that dictates treatment in order to minimize adverse side effects, such as renal failure, quick determination of MIC is of paramount importance. Thus, we first examined if the presence of antibiotics in the media might induce non-specific nanoparticle clustering, potentially interfering with the assay��s carbohydrate specificity. In these control studies, a bacterial population which is typically used in MIC experiments was incubated in the presence of different antibiotic concentrations. Results showed that these culture conditions did not affect the spin-spin relaxation times of the nanoparticle solution, indicating absence of non-specific antibiotic-mediated nanoparticle assembly. Subsequently, we examined if bacterial growth and the corresponding carbohydrate uptake are affected by the presence of a particular antibiotic. After incubating E. coli for 2 hours in the presence of ampicillin, we took 10-mL bacterial culture aliquots in order to examine them using the dextrancoated polysaccharide nanosensors. Thirty minutes after addition of Con A distinct changes in the T2 were observed, indicating the presence of two cohorts. Specifically, the starch utilization and growth of E. coli were suppressed at ampicillin concentrations above 8 mg, as demonstrated by the low changes in the DT2 compared to the sterile medium. Furthermore, the nanoparticle-derived MIC of 8 mg was confirmed through the turbidity method, which is the current gold standard for antimicrobial susceptibility determination. Although both assays provided identical results, the dextran-coated polysaccharide nanosensor assay yielded faster results with an overall time of 2.5 hours, as XL880 c-Met inhibitor opposed to 24 hours. In addition, the nanosensor-based assay requires smaller bacterial culture volumes as opposed to the turbidity MIC method. The latter is of particular logistics importance during epidemics and drug discovery efforts, as it facilitates the simultaneous and cost-effective screening of multiple samples, eliminating the need of tedious Everolimus visual examination of numerous cultures. Subsequently, we further validated the antimicrobial susceptibility potential of dextran-coated polysaccharide nanosensors using other bacteria. Shigella sonnie, a close relative of the highly pathogenic and Shiga-toxin producer Shigella dysenteriae, had an ampicillin MIC of 8 mg. Similar to E. coli, these results were also obtained within 2.5 hours. Then, we investigated if our assay can determine bacterial drug resistance via the changes in spin-spin relaxation time.

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