Project description:Methicillin-resistant Staphylococcus aureus is one of the major causative agents associated to infections with a high morbidity and mortality in hospitals worldwide. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin isolated and characterized from Larrea tridentata showed the best activity towards methicillin-resistant S. aureus. Understanding of mechanism of action of drugs allows design drugs in a better way. Therefore, we employed microarray to obtain gene expression profile of methicillin-resistant S. aureus after exposure to 3'-demethoxy-6-O-demethylisoguaiacin. The results showed that lignan had an effect on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death.
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) infections result in more than 200,000 hospitalizations and 10,000 deaths in the United States each year and remain an important medical challenge. To better understand the transcriptome of Staphylococcus aureus USA300 NRS384, a community-acquired MRSA strain, we have conducted an RNA-Seq experiment on WT samples.
Project description:Methicillin-resistant Staphylococcus aureus is one of the major causative agents associated to infections with a high morbidity and mortality in hospitals worldwide. In previous studies, we reported that lignan 3'-demethoxy-6-O-demethylisoguaiacin isolated and characterized from Larrea tridentata showed the best activity towards methicillin-resistant S. aureus. Understanding of mechanism of action of drugs allows design drugs in a better way. Therefore, we employed microarray to obtain gene expression profile of methicillin-resistant S. aureus after exposure to 3'-demethoxy-6-O-demethylisoguaiacin. The results showed that lignan had an effect on cell membrane affecting proteins of the ATP-binding cassette (ABC) transport system causing bacteria death. This study consisted of comparison of isolated RNA of MRSA not treated and MRSA treated with lignan 3'-demethoxy-6-O-demethylisoguaiacin. Both RNAs samples were differentially dyed with Cy3 and Cy5 during cDNA synthesis and hybridized on DNA chip. Afterwards, the chip was scanned in a GenePix 4000B scanner. The resulting gene expression profile was analyzed in databases for functional annotations to find a potential mechanism of the lignan in MRSA.
Project description:Background: Telavancin is a novel semi-synthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria including Staphylococcus aureus strains resistant to methicillin or vancomycin. This study describes transcriptome alterations in S. aureus strain ATCC29213 treated with telavancin for 15 min and 60 min in comparing with other agents treatment, including vancomycin, enduracidin, m-chlorophenylhydrazone.
Project description:Resolving chromatin remodeling-linked gene expression changes is important for understanding disease states. We describe MAGICAL (Multiome Accessible Gene Integration Calling And Looping), a hierarchical Bayesian approach that leverages paired scRNA-seq and scATAC-seq data from different conditions to map disease-associated transcription factors, regulatory sites and genes as regulatory circuits. By introducing hidden Bayesian variables to allow modeling noise and signal variation across cells and conditions in both transcriptome and chromatin data, in systemic evaluations MAGICAL achieved high accuracy on circuit prediction at cell-type resolution. We applied MAGICAL to study Staphylococcus aureus sepsis from peripheral blood mononuclear single cell data that we generated from infected subjects and healthy uninfected controls. MAGICAL identified sepsis-associated regulatory circuits predominantly in CD14 monocytes, known to be sepsis activated. We addressed the challenging problem of distinguishing methicillin-resistant- (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections, where differential expression analysis failed to show predictive value. MAGICAL, however, identified epigenetic circuit biomarkers that distinguished MRSA from MSSA.
Project description:Resolving chromatin remodeling-linked gene expression changes is important for understanding disease states. We describe MAGICAL (Multiome Accessible Gene Integration Calling And Looping), a hierarchical Bayesian approach that leverages paired scRNA-seq and scATAC-seq data from different conditions to map disease-associated transcription factors, regulatory sites and genes as regulatory circuits. By introducing hidden Bayesian variables to allow modeling noise and signal variation across cells and conditions in both transcriptome and chromatin data, in systemic evaluations MAGICAL achieved high accuracy on circuit prediction at cell-type resolution. We applied MAGICAL to study Staphylococcus aureus sepsis from peripheral blood mononuclear single cell data that we generated from infected subjects and healthy uninfected controls. MAGICAL identified sepsis-associated regulatory circuits predominantly in CD14 monocytes, known to be sepsis activated. We addressed the challenging problem of distinguishing methicillin-resistant- (MRSA) and methicillin-sensitive Staphylococcus aureus (MSSA) infections, where differential expression analysis failed to show predictive value. MAGICAL, however, identified epigenetic circuit biomarkers that distinguished MRSA from MSSA.
