Staphylococcus aureus
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ABSTRACT:
PROVIDER: PRJNA144047 | ENA |
REPOSITORIES: ENA
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Project description:The alternative sigma factor M-OM-^CB of Staphylococcus aureus is involved in the coordination of the general stress response, expression of virulence determinants and modulation of antibiotic resistance levels. It controls a large regulon, either directly by recognizing conserved M-OM-^CB promoter sequences, or indirectly via M-OM-^CB-dependent elements. The M-OM-^CB-controlled yabJ-spoVG operon encodes two such putative downstream elements. We report here transcriptome analysis in S. aureus Newman showing that inactivation of the yabJ-spoVG operon had primarily a repressing effect on a small subregulon comprising mainly virulence factors, including a nuclease (nuc), a protease (splE) and a lipase (lip).. As a consequence extracellular nuclease, protease and lipase activities were reduced in a yabJspoVG mutant. Trans-complementation by SpoVG was sufficient to restore their reduced phenotypic expression and lowered transcription due to yabJ-spoVG deletion. It did not restore, however, the changes triggered by M-OM-^CB inactivation, indicating that both regulons do only partially overlap, despite the M-OM-^CB dependency of the yabJ-spoVG expression. Thus, M-OM-^CB is likely to control additional, SpoVG-independent factors affecting the expression of numerous hydrolytic enzymes. SpoVG, on the other hand, seems to fine-tune the M-OM-^CB-dependent regulation of a subset of virulence factors by antagonizing the M-OM-^CB effect. Newman wild type strain compared to double mutant spoVG and yabJ or to sigB truncated mutant
2011-11-23 | E-GEOD-30115 | biostudies-arrayexpress
Project description:The alternative sigma factor σB of Staphylococcus aureus is involved in the coordination of the general stress response, expression of virulence determinants and modulation of antibiotic resistance levels. It controls a large regulon, either directly by recognizing conserved σB promoter sequences, or indirectly via σB-dependent elements. The σB-controlled yabJ-spoVG operon encodes two such putative downstream elements. We report here transcriptome analysis in S. aureus Newman showing that inactivation of the yabJ-spoVG operon had primarily a repressing effect on a small subregulon comprising mainly virulence factors, including a nuclease (nuc), a protease (splE) and a lipase (lip).. As a consequence extracellular nuclease, protease and lipase activities were reduced in a yabJspoVG mutant. Trans-complementation by SpoVG was sufficient to restore their reduced phenotypic expression and lowered transcription due to yabJ-spoVG deletion. It did not restore, however, the changes triggered by σB inactivation, indicating that both regulons do only partially overlap, despite the σB dependency of the yabJ-spoVG expression. Thus, σB is likely to control additional, SpoVG-independent factors affecting the expression of numerous hydrolytic enzymes. SpoVG, on the other hand, seems to fine-tune the σB-dependent regulation of a subset of virulence factors by antagonizing the σB effect.
2011-11-23 | GSE30115 | GEO
Project description:Staphylococcus aureus is one of the first and most prevalent pathogens cultured from the airways of cystic fibrosis (CF) patients, which can persist there for extended periods. Airway infections in CF patients are characterized by a strong inflammatory response of highly recruited neutrophils. One killing mechanism of neutrophils is the formation of neutrophil extracellular traps (NETs), which capture and eradicate bacteria by extracellular fibers of neutrophil chromatin decorated with antimicrobial granule proteins. S. aureus secretes nuclease, which can degrade NETs. We hypothesized, that S. aureus adapts to the airways of CF patients during persistent infection by escaping from NET-mediated killing via an increase of nuclease activity. Sputum samples of CF patients with chronic S. aureus infection were visualized by confocal microscopy after immuno-fluorescence staining for NET-specific markers, S. aureus bacteria and overall DNA structures. Nuclease activity was analyzed in sequential isogenic long persisting S. aureus isolates, as confirmed by whole genome sequencing, from an individual CF patient using a FRET-based nuclease activity assay. Additionally, some of these isolates were selected and analyzed by qRT-PCR to determine the expression of nuc1 and regulators of interest. NET-killing assays were performed with clinical S. aureus isolates to evaluate killing and bacterial survival depending on nuclease activity. To confirm the role of nuclease during NET-mediated killing, a clinical isolate with low nuclease activity was transformed with a nuclease expression vector (pCM28nuc). Furthermore, two sputa from an individual CF patient were subjected to RNA-sequence analysis to evaluate the activity of nuclease in vivo. In sputa, S. aureus was associated to extracellular DNA structures. Nuclease activity in clinical S. aureus isolates increased in a time-and phenotype-dependent manner. In the clinical isolates, the expression of nuc1 was inversely correlated to the activity of agr and was independent of saeS. NET-mediated killing was significantly higher in S. aureus isolates with low compared to isolates with high nuclease activity. Importantly, transformation of the clinical isolate with low nuclease activity with pCM28nuc conferred protection against NET-mediated killing confirming the beneficial role of nuclease for protection against NETs. Also, nuclease expression in in vivo sputa was high, which underlines the important role of nuclease within the highly inflamed CF airways. In conclusion, our data show that S. aureus adapts to the neutrophil-rich environment of CF airways with increasing nuclease expression most likely to avoid NET-killing during long-term persistence.
2019-11-01 | GSE139662 | GEO
Project description:Staphylococcus aureus produces the cyclic dipeptides tyrvalin and phevalin (aureusimine A and B, respectively). A previous study reported that S. aureus mutants not capable of producing these compounds were less virulent in vivo through the deranged regulation of virulence factor genes. These findings, however, have been questioned as an unknown mutation in an operon that regulates virulence was discovered in the mutant strain. Here, we report that S. aureus biofilms produce greater amounts of phevalin than their planktonic counterparts. When administered to human keratinocytes, phevalin had no substantial effect on gene expression. Phevalin had no obvious impact on the extracellular metabolome of S. aureus. However, conditioned medium from S. aureus spiked with phevalin resulted in significant differences in keratinocyte gene expression compared to conditioned medium alone. A role for phevalin in manipulating host responses is apparent. Additionally, phevalin is a potential biomarker and/or therapeutic target for chronic, biofilm-based infections. Secreted factors from S. aureus biofilm and planktonic cultures with equivalent population sizes were placed in contact with human HaCaT keratinocytes for 4 hours. Keratinocytes were grown to ~90% confluency.
2012-10-01 | E-GEOD-32920 | biostudies-arrayexpress
Project description:Staphylococcus aureus produces the cyclic dipeptides tyrvalin and phevalin (aureusimine A and B, respectively). A previous study reported that S. aureus mutants not capable of producing these compounds were less virulent in vivo through the deranged regulation of virulence factor genes. These findings, however, have been questioned as an unknown mutation in an operon that regulates virulence was discovered in the mutant strain. Here, we report that S. aureus biofilms produce greater amounts of phevalin than their planktonic counterparts. When administered to human keratinocytes, phevalin had no substantial effect on gene expression. Phevalin had no obvious impact on the extracellular metabolome of S. aureus. However, conditioned medium from S. aureus spiked with phevalin resulted in significant differences in keratinocyte gene expression compared to conditioned medium alone. A role for phevalin in manipulating host responses is apparent. Additionally, phevalin is a potential biomarker and/or therapeutic target for chronic, biofilm-based infections.
2012-10-01 | GSE32920 | GEO
Project description:Survival and pathogenesis of Staphylococcus aureus in the host requires the ability to respond to changes. Therefore, tight regulation of gene expression via various regulators is essential. Also, the organization of genes in operons is of influence on the regulation of gene expression. Knowledge of gene expression under different conditions and the ability to accurately predict operons are important steps towards understanding the transcriptional regulation, function and pathogenesis. A whole genome Agilent microarray was developed for the highly virulent, community-acquired MSSA476.During standard growth in a defined medium, we were able to determine four basic gene expression patterns of S. aureus for both virulence and non-virulence genes. In addition, we predicted operon structures by calculating Pearson correlation coefficients of the transcriptional profiles for all adjacent probes over all time points and replicas. In this study, we have set a basis for the knowledge on gene expression of MSSA476 during growth. Moreover, the correlation of time-dependent transcriptional profiles of adjacent probes seems to be a promising approach to predict operon structures. Five separate cultures of S. aureus mssa476 were grown. Of each replicate culture, samples were taken at 1, 2, 3, 4, 5, 6 and 9 h post inoculation (p.i.). In total, this amounts to 35 samples (7 time points in 5 replicates).
2010-06-24 | E-GEOD-16488 | biostudies-arrayexpress
Project description:Staphylococcus aureus is one of the most important pathogens in humans and animals, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. Rhein, a natural plant product, has potential antimicrobial activity against Staphylococcus aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with rhein. Results provided insight into mechanisms involved in rhein - Staphylococcus aureus interactions. Keywords: rhein response
2007-06-15 | GSE8135 | GEO
Project description:Survival and pathogenesis of Staphylococcus aureus in the host requires the ability to respond to changes. Therefore, tight regulation of gene expression via various regulators is essential. Also, the organization of genes in operons is of influence on the regulation of gene expression. Knowledge of gene expression under different conditions and the ability to accurately predict operons are important steps towards understanding the transcriptional regulation, function and pathogenesis. A whole genome Agilent microarray was developed for the highly virulent, community-acquired MSSA476.During standard growth in a defined medium, we were able to determine four basic gene expression patterns of S. aureus for both virulence and non-virulence genes. In addition, we predicted operon structures by calculating Pearson correlation coefficients of the transcriptional profiles for all adjacent probes over all time points and replicas. In this study, we have set a basis for the knowledge on gene expression of MSSA476 during growth. Moreover, the correlation of time-dependent transcriptional profiles of adjacent probes seems to be a promising approach to predict operon structures.
2010-01-25 | GSE16488 | GEO
Project description:Staphylococcus aureus is one of the most important pathogens in humans and animals, multiply resistant strains are increasingly widespread, new agents are needed for the treatment of S. aureus. Rhein, a natural plant product, has potential antimicrobial activity against Staphylococcus aureus. We employed Affymetrix Staphylococcus aureus GeneChipsTM arrays to investigate the global transcriptional profiling of Staphylococcus aureus ATCC25923 treated with rhein. Results provided insight into mechanisms involved in rhein - Staphylococcus aureus interactions. Keywords: rhein response Staphylococcus aureus cells were exposed for 45 minutes to rhein at concentration of 8 µg/ml (1/2à MIC), 6 samples including 3 control samples are analyzed.
2010-06-10 | E-GEOD-8135 | biostudies-arrayexpress
Project description:In this study we mutated the ecsAB operon in two different Staphylococcus aureus strains, Newman and LS-1, and performed a wide characterization of phenotypic effects of the mutations. A growth defect, increased autolysis and lysostaphin sensitivity, decreased levels of cell wall proteins and altered cell surface texture indicate that Ecs deficiency causes significant changes in the cell wall. The precursor form of staphylokinase was released into the wall in an Ecs-dependent manner. Pathogenicity of the ecs mutants was studied with a mouse arthritis model. Mice inoculated with ecs mutants developed markedly milder infections than when inoculated with the wild-type strains, as was illustrated by a lower mortality, less weight loss, decreased persistence of staphylococci in the kidneys and a milder arthritis. DNA microarray analysis revealed that inactivation of Ecs in S. aureus Newman caused either up-regulation or down-regulation of genes encoding various membrane transport proteins, particularly ABC transporters and phosphate-specific transport (PST) systems. Differentially expressed were also several genes encoding proteins involved in virulence, including the virulence factor regulator protein Rot, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Furthermore, the susceptibility of ecs mutant to ribosomal antibiotics as well as the chelerythrine and sanguinarine plant alkaloids was increased. WT and ecsA mutant strains were hybridized at 3 and 6 hours of growth in rich medium (4-replicates)
2011-01-01 | E-GEOD-22353 | biostudies-arrayexpress