MouR controls the expression of the Listeria monocytogenes Agr system and mediates virulence
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ABSTRACT:
ORGANISM(S): Listeria monocytogenes EGD-e
PROVIDER: GSE106833 | GEO | 2018/10/22
REPOSITORIES: GEO
Similar Datasets
Project description:The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant Wild type in triplicate is compared to mutant in triplicate totalling 27 samples
2010-05-14 | E-GEOD-10165 | biostudies-arrayexpress
Project description:The Staphylococcus aureus accessory gene regulator (agr) is a prototype quorum-sensing system in Gram-positive bacteria and a paradigmatic example of gene regulation by a small regulatory RNA, RNAIII. Using genome-wide transcriptional profiling in the community-associated methicillin-resistant (CA-MRSA) strain MW2, we demonstrate here that in contrast to the current model of target gene regulation by agr, a large subset of agr-regulated genes is controlled independently of RNAIII. This group comprised predominantly metabolism genes, whereas virulence factors were mostly controlled by RNAIII. Remarkably, the phenol-soluble modulin (PSM) leukocidin genes were the only virulence determinants under RNAIII-independent control, emphasizing their exceptional role in S. aureus physiology and pathogenesis. Of note, PSM promoters bound the AgrA response regulator protein, previously believed to interact exclusively with agr promoters, explaining the exceptionally strict control of PSMs by agr. Our results suggest that virulence factor control is a secondary acquisition of the agr regulon, which evolved by development of RNAIII around the mRNA of the PSM d-toxin, exemplifying how gene control via a small regulatory RNA may be linked to a pre-established regulatory circuit. In addition to elucidating agr control in CA-MRSA, which revealed features potentially crucial for CA-MRSA pathogenesis, our study establishes a novel two-level model of cell-density dependent gene regulation in S. aureus and gives important insight into the connection of metabolism and virulence control in this leading opportunistic pathogen. Keywords: Wild type control vs mutant
2009-01-05 | GSE10165 | GEO
Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant Wild type vs mutant agr strains.
2011-03-29 | E-GEOD-18793 | biostudies-arrayexpress
Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant
2011-03-29 | GSE18793 | GEO
Project description:RNAseq of exponentially growing cultures of the four agr prototype strains used in the study to investigate if differential expression of regulators interacting with the agr system could explain the differences in AIP sensitivity. Abstract Staphylococcus aureus both colonizes humans and causes severe virulent infections. Virulence is regulated by the agr quorum sensing system and its autoinducing peptide (AIP), with dynamics at the single-cell level across four agr-types – each defined by distinct AIP sequences and capable of cross-inhibition – remaining elusive. Employing microfluidics, time-lapse microscopy, and deep-learning image analysis, we uncovered significant differences in AIP sensitivity among agr-types. We observed bimodal agr activation, attributed to intergenerational phenotypic stability and influenced by AIP concentration. Upon AIP stimulation, agr III showed AIP insensitivity, while agr II exhibited increased sensitivity and prolonged generation time. Beyond expected cross-inhibition of agr I by heterologous AIP II and III, the presumably cross-activating AIP IV also inhibited agr I. Community interactions across different agr-type pairings revealed four main patterns: stable or switched dominance, and delayed or stable dual activation, influenced by community characteristics. These insights underscore the potential of personalized treatment strategies considering virulence and genetic diversity.
2024-03-05 | E-MTAB-13859 | biostudies-arrayexpress
Project description:The study aims to compare gene expression patterns of Staphyloccoccus aureus USA300 wild type (reference) vs USA300 agr knockout(query). The agr quorum sensing system is an important regulator of density dependent gene expression. To determine the role of agr in USA300 virulence a agr mutant was constructed and differential gene expression compared to the parental wildtype.
2011-04-08 | GSE26254 | GEO
Project description:The agr quorum-sensing system clearly links Staphylococcus aureus metabolism to virulence, but little is known about how agr alters metabolism to affect cell survival during severe stress. Recently, we reported that agr activity increases survival of bacteria during treatment with lethal concentrations of H2O2, a crucial host defense against S. aureus. Here we report that protection by agr extends to growth resumption during the exit from stationary phase. The data indicate that the agr functionality of a cell’s ancestor affects stress-resiliency after resuming growth. Protection against killing by H2O2 depended on the agr effector molecule RNAIII and Rot, a transcription factor targeted by RNAIII. Expression data revealed that Δagr strains shift to fermentation, suggesting that agr promotes aerobic respiration. Epistasis between mutation of agr and sortase, which anchors surface proteins to the cell wall, suggested that reduced killing by H2O2 of wild-type agr strains acts through down-regulation of surface proteins that perturb respiration. Respiration generates reactive oxygen species (ROS), moderate amounts of which can protect from subsequent challenge by lethal concentrations, explaining agr-mediated protection against subsequent lethal H2O2 doses. Increased survival of wild-type agr cells in response to H2O2 required sodA, which dismutates O2- to H2O2, suggesting that sodA helps induce the low, protective levels of ROS triggered by agr. Additionally, detrimental effects of the Δagr mutation require ahpC, which functions to decrease the intracellular level of H2O2. Deletion of ahpC or sortase attenuated neutrophil-mediated killing of Δagr strains, demonstrating the importance of priming in anticipation of impending immune attack.
2023-06-20 | GSE206916 | GEO
Project description:The agr quorum-sensing system clearly links Staphylococcus aureus metabolism to virulence, but little is known about how agr alters metabolism to affect cell survival during severe stress. Recently, we reported that agr activity increases survival of bacteria during treatment with lethal concentrations of H2O2, a crucial host defense against S. aureus. Here we report that protection by agr extends to growth resumption during the exit from stationary phase. The data indicate that the agr functionality of a cell’s ancestor affects stress-resiliency after resuming growth. Protection against killing by H2O2 depended on the agr effector molecule RNAIII and Rot, a transcription factor targeted by RNAIII. Expression data revealed that Δagr strains shift to fermentation, suggesting that agr promotes aerobic respiration. Epistasis between mutation of agr and sortase, which anchors surface proteins to the cell wall, suggested that reduced killing by H2O2 of wild-type agr strains acts through down-regulation of surface proteins that perturb respiration. Respiration generates reactive oxygen species (ROS), moderate amounts of which can protect from subsequent challenge by lethal concentrations, explaining agr-mediated protection against subsequent lethal H2O2 doses. Increased survival of wild-type agr cells in response to H2O2 required sodA, which dismutates O2- to H2O2, suggesting that sodA helps induce the low, protective levels of ROS triggered by agr. Additionally, detrimental effects of the Δagr mutation require ahpC, which functions to decrease the intracellular level of H2O2. Deletion of ahpC or sortase attenuated neutrophil-mediated killing of Δagr strains, demonstrating the importance of priming in anticipation of impending immune attack.
2023-06-20 | GSE206889 | GEO
Project description:These cultures were grown to examine the differences in Agr-regulated virulence factor gene expression between wild-type S. aureus FRI1169 and a non-hemolytic variant isolated from a biofilm inoculated with FRI1169. The study is described more thoroughly in the paper "Generation of virulence factor variants in Staphylococcus aureus biofilms", Yarwood et al., J. Bacteriol. 2007. Keywords: Wild-type versus mutant comparison, single time-point
2007-09-01 | GSE8482 | GEO
Project description:The purpose of this study was to compare the global, growth phase-dependent transcriptional profiles of two isolates of Staphylococcus aureus. One isolate is a prototypic laboratory strain named RN6390, and has been used frequently as a model organism for study of staphylococcal physiology and virulence. However, recent studies indicate that RN6390 is not, in general, genotypically or phenotypically representative of clinical isolates of Staphyloccos aureus. Therefore, there is no current comprehensive picture of gene expression patterns in a virulent, clinical isolate of Staphyloccous aureus. For these reasons, we compare the transcriptional profile of RN6390 to that of a virulent clinical isolate, UAMS-1. Also included in this study is profiling of two UAMS-1 regulatory mutants, UAMS-155, and UAMS-929. These strains possess mutations in the accessory gene regulator (agr) and staphylococcal accessory regulator (sarA) genes, respectively. These two genes are well described global regulatory molecules that are reported to play important roles in controlling virulence factor production and biofilm formation in Staphylococcus aureus. However, most study of these two molecules has been limited to laboratory strains such as RN6390. For these reasons, this study also includes transcriptional profiling of UAMS agr and sarA mutants. Keywords: Comparative, growth phase-dependent transcriptional profiling of bacterial strains and isogenic regulatory mutants
2006-10-03 | GSE5466 | GEO