Project description:Vancomycin-resistant Enterococcus faecium (VREfm) is a leading cause of healthcare-associated infections globally and demands new approaches for treatment. Here we show that genetic and pharmacological inactivation of a highly conserved NlpC/P60 peptidoglycan hydrolase, secreted antigen A (SagA), enhanced vancomycin susceptibility of VREfm ex vivo and in vivo. Notably, genetic deletion of sagA impaired VREfm peptidoglycan remodeling, growth and increased the activity of vancomycin. We then identified first-in-class covalent NlpC/P60 peptidoglycan hydrolase inhibitors and demonstrated that pharmacological inactivation of SagA activity also impaired peptidoglycan remodeling and increased the efficacy of vancomycin in several VREfm clinical isolates. Our study reveals peptidoglycan hydrolases are druggable targets whose inactivation improves the efficacy of vancomycin against VREfm.
Project description:This SuperSeries is composed of the following subset Series: GSE26877: Nprl3 is Required for Normal Development of the Cardiovascular System GSE27918: Genome-wide maps of chromatin state in mouse erythroid cells. GSE27919: Genome-wide map of DNaseI hypersensitivity in mouse erythroid cells. GSE27920: Transcriptiome of mouse erythroid cells (part2) Refer to individual Series
Project description:ngs2012_02_microd-ngs microd-part2-Effect of dilution on RNA seq sensitivity-One sample of total RNA extracted from whole embryo by laser assisted microdissection was diluted from 5ng to 10pg to check sensitivity of the library construction and subsequent sensitivity of transcript identification by RNA seq.
