Project description:Hybridisation of reference strains to the VirEp Staphylococcus aureus microarray, and characterisation of different S. aureus isolates from different locations and associated with different diseases.
Project description:Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) mutant S. aureus strains.
Project description:Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) which has been shown to increase the susceptibility of various bacteria to antimicrobials and demonstrated to have broad antimicrobial activity. This study describes transcriptome alterations in S. aureus strain COL grown with diclofenac and characterizes the effects of this NSAID on antibiotic susceptibility in laboratory, clinical and diclofenac reduced-susceptibility (DcRS) mutant S. aureus strains.
Project description:To identify potential targets of co-regulation by DnaA and Rok, we compared the transcriptional profiles of dnaA null, rok null, and dnaA null rok null mutants. Because a dnaA null mutant requires an oriC- strain background, we used an oriC- oriN+ background for all strains, to allow direct comparisons.
Project description:We used high-throughput qRT-PCR analysis to obtain full genome qRT- PCR data for the Staphylococcus aureus strains USA300 (wild type) and TB15 (mutant). Both strains were collected during infection from 4 mouse organs ( skin, kidney, lung,liver) as well as from human neutrophil infection.
Project description:The S. aureus transcriptome was assessed for strains Newman (wild type) and Newman (sarZ) during both exponential (2hr) and early stationary (5hr) cell growth.
Project description:This analysis is part of the study Whole-transcriptome analysis of Staphylococcus aureus under laboratory and infection-mimicking conditions (Mäder, Nicolas et al., to be submitted) where the S. aureus HG001 transcriptome was analyzed under more than 40 different biological conditions. The data revealed a relatively low abundance of antisense RNAs in S. aureus, overlapping only 6% of the coding genes. Transcriptome analysis of the rho deletion mutant revealed a remarkable overall increase in antisense transcription in S. aureus.
Project description:Staphylococcus aureus is a pulmonary pathogen associated with substantial human morbidity and mortality. As vaccines targeting virulence determinants have failed to be protective in humans, other factors are likely involved in pathogenesis. Here we analysed transcriptomic responses of human clinical isolates of S. aureus from initial and chronic infections. We observed upregulated collagenase and proline transporter gene expression in chronic infection isolates. Metabolomics of bronchiolar lavage fluid, fibroblast infection, growth assays and analysis of bacterial mutant strains showed that airway fibroblasts produce collagen during S. aureus infection. Host-adapted bacteria upregulate collagenase, which degrades collagen and releases proline. S. aureus then imports proline, which fuels oxidative metabolism via the tricarboxylic acid cycle. Proline metabolism provides host-adapted S. aureus with a metabolic benefit enabling out-competition of non-adapted strains. These data suggest that clinical settings characterized by airway repair processes and fibrosis provide a milieu that promotes S. aureus adaptation and supports infection.
Project description:The S. aureus transcriptome was assessed for strains Newman (wild type) and Newman (sarZ) during both exponential (2hr) and early stationary (5hr) cell growth. The S. aureus transcriptome was assessed for strains Newman (wild type) and Newman (sarZ) during both exponential (2hr) and early stationary (5hr) cell growth. The experiment was performed in duplicate or triplicate, and RNA samples labeled/hybridized to independent commercially available Affymetrix GeneChips
Project description:Nitric oxide synthase (NOS) enzymes produce nitric oxide (NO), a highly reactive free radical capable of interacting with multiple cellular targets. Although saNOS contributes to Staphylococcus aureus virulence, as well as protection against exogenous oxidative stress and antimicrobials, the current mechanism behind these phenotypes is unknown. Here we report a previously-undescribed role for saNOS in modulating S. aureus physiology. When grown aerobically, endogenous reactive oxygen species (ROS) and superoxide levels were elevated in a S. aureus nos mutant. NO has been shown to slow respiration in other organisms, and likewise, comparison of respiratory dehydrogenase activity and membrane potential in wild-type, nos mutant, and complement strains suggested that saNOS-derived NO limits S. aureus aerobic respiration. Multiple transcriptional and metabolic changes were also observed in a S. aureus nos mutant, as assessed by RNAseq and targeted metabolomics analyses, respectively. Specifically, expression of genes associated with oxidative and nitrosative stress responses, anaerobic and lactate metabolism, and cytochrome biosynthesis and assembly were increased in the nos mutant relative to wild-type. Metabolites utilized to produce reducing equivalents by the right arm of the TCA cycle were depleted in a nos mutant (citrate and α-ketoglutarate), whereas fumarate and malate levels were increased relative to wild-type and complement strains. A significant reduction in lactate levels was also observed in the nos mutant. Collectively, these results support a model in which the absence of saNOS results in increased respiration and ROS accumulation, which may signal the cells to switch to an alternative lactate-based respiratory metabolism.
