Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Insights into the Staphylococcus aureus-host interface: global changes in host and pathogen gene expression in a rabbit skin infection model

ABSTRACT: Staphylococcus aureus is an important cause of human skin and soft tissue infections (SSTIs) globally. Notably, 80% of all SSTIs are caused by S. aureus, of which ~63% are abscesses and/or cellulitis. Although progress has been made, our knowledge of the host and pathogen factors that contribute to the pathogenesis of SSTIs is incomplete. To provide a more comprehensive view of this process, we monitored changes in the S. aureus transcriptome and selected host proinflammatory molecules during abscess formation and resolution in a rabbit skin infection model. Within the first 24 h, S. aureus transcripts involved in DNA repair, metabolite transport, and metabolism were up regulated, suggesting an increase in the machinery encoding molecules involved in replication and cell division. There was also increased expression of genes encoding virulence factors, namely secreted toxins and fibronectin and/or fibrinogen-binding proteins. Of the host genes tested, we found that transcripts encoding host IL-8, IL1β, oncostatin M-like, CCR1, CXCR1 (IL8RA), CCL4 (MIP-1β) and CCL3 (MIP1α)-like proteins were among the most highly up-regulated transcripts during S. aureus abscess formation. Our findings provide additional insight into the pathogenesis of S. aureus SSTIs, including a temporal component of the host response. These results serve as a springboard for future studies directed to better understand how/why mild or moderate SSTIs progress to invasive disease.

ORGANISM(S): Staphylococcus aureus subsp. aureus USA300 Staphylococcus aureus

PROVIDER: GSE61669 | GEO | 2017/02/10

SECONDARY ACCESSION(S): PRJNA261800

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Spatially-targeted proteomics of S. aureus abscess formation

Project description:Staphylococcus aureus is a major contributor of healthcare-associated infections and able to withstand numerous frequently used antibiotics. In order to develop novel treatment approaches, a deeper understanding of the complex interaction between host and pathogen is required. This is particularly true for the processes during development of tissue abscesses, which are important contributors to acute and persistent staphylococcal infections. Notably, the formation of staphylococcal abscesses takes place in distinct stages. Consequently, studies aiming to elucidate the underlying mechanisms of abscess development have to take temporal and spatial components into account. State-of-the-art proteomic technologies offer insight into complex biological systems. However, the pairing of spatial information and deep proteomic analysis is challenging, complicating the targeted analysis of relatively small-scale and heterogeneous structures like organ abscesses. To overcome existing technical limitations, we have previously introduced the use of a spatially targeted liquid extraction surface analysis (LESA) workflow termed “microLESA”. In our current study, we perform microLESA to investigate the processes at the host-pathogen interface during development of staphylococcal kidney abscesses in a murine model of systemic infection. For this investigation, regions from the abscess community, the interface surrounding the abscess, and the cortex of infected kidneys were extracted and analyzed at both 4- and 10-days post infection. By defining the proteome of different abscess regions across the course of infection, we followed the immune response and bacterial contribution to abscess development through spatial and temporal proteomic changes. The information gathered was then mapped through pathway analysis to characterize the metabolic processes at the host-pathogen interface during staphylococcal infection.

2020-11-30 | PXD019920 | Pride

Linoleic Acid Stimulation of WT Staphylococcus aureus USA300 NRS384

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. A key factor of S. aureus pathogenesis is the production of virulence proteins that are secreted into the extracellular matrix damaging host tissues and forming abscesses that may serve as replicative niches for the bacteria. We recently discovered that host-derived cis-unsaturated fatty acids activate the transcription and translation of EsxA, a protein that plays a central role in abscess formation in clinically relevant MRSA strains. Additionally, we discovered that fatty acid stimulation of EsxA is dependent on fakA, a gene that encodes a protein responsible for the incorporation of exogenous fatty acids into the S. aureus phospholipid membrane. In order to gain a comprehensive understanding of host-fatty-acid-sensing in S. aureus, we performed RNA-Seq analysis on WT Staphylococcus aureus USA300 NRS384, a community-acquired MRSA strain, in the presence and absence of 10μM linoleic acid.

2017-11-15 | GSE101580 | GEO

Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice

Project description:Neutrophil abscess formation is critical in innate immunity against many pathogens. Here, the mechanism of neutrophil abscess formation was investigated using a mouse model of Staphylococcus aureus cutaneous infection. Gene expression analysis of S. aureus-infected skin revealed that induction of neutrophil recruitment genes was largely dependent upon IL-1beta/IL-1R activation. Unexpectedly, using IL 1beta reporter mice, neutrophils were identified as the primary source of IL-1beta at the site of infection. Furthermore, IL-1beta-producing neutrophils were necessary and sufficient for abscess formation and bacterial clearance. S. aureus-induced IL 1beta production by neutrophils required TLR2, NOD2, FPRs and the ASC/NLRP3 inflammasome. Taken together, IL-1beta and neutrophil abscess formation during an infection are functionally, spatially and temporally linked as a consequence of direct IL-1beta production by neutrophils. Lesional skin biopsies obtained from C57BL/6J WT mice or IL-1R-deficient mice at 4 hours post-infection with Staphylococcus aureus. Uninfected skin biopsies were also collected from WT and IL-1R-deficient mice.

2012-12-05 | E-GEOD-36826 | biostudies-arrayexpress

Neutrophil-derived IL-1β is sufficient for abscess formation in immunity against Staphylococcus aureus in mice

2012-12-05 | GSE36826 | GEO

Genomic comparisons of USA300 Staphylococcus aureus colonizating the nose and rectum of children with skin abscesses

Project description:USA300 Staphylococcus aureus is responsible for the current outbreak of skin abscesses in the United States. Unlike other USA types, USA300 colonizes the rectum at rates higher than the nose. The reason for the difference in colonization site preference may be related to specific adherence or attachment factors contained in the genome of these strains. Additional knowledge in this field may help design novel prophylactic and therapeutic strategies to combat staphylococcal infections. Strains of USA300 MSSA and MRSA colonizing the nose and/or rectum from children with staphylococcal skin abscesses were compared by whole genome array technology to identify bacterial genetic determinants associated with site-specific colonization. Strains isolated from different colonization sites were indistinguishable by genomic content. Site-specific colonization traits were not detected in the colonizing bacteria by this array. Either host characteristics associated with staphylococcal carriage or under represented bacterial genomic constructions need to be examined to determine the etiology of this site-specific colonization. Data is also available from <ahref=http://bugs.sgul.ac.uk/E-BUGS-102 target=_blank>BuG@Sbase</a>

2011-04-15 | E-BUGS-102 | biostudies-arrayexpress

The Staphylococcus aureus Host Cell Genetic Adhesion Network

Project description:Adhesion of Staphylococcus aureus to the host’s skin and mucosae enables asymptomatic colonization and the establishment of infections. This process is facilitated by cell wall-anchored (CWA) adhesins that are covalently attached to the bacterial cell wall and exhibit affinity for host ligands. To gain insight into the cellular factors contributing to adhesion, we developed a sensitive and robust assay to enable the large-scale profiling of S. aureus adhesion to host ligands. Using this assay, we profiled a sequence defined transposon mutant library of the community-associated methicillin-resistant S. aureus (CA-MRSA) isolate USA300, to identify mutant strains with attenuated adhesion to human derived keratin, fibronectin and fibrinogen. Overall, we identified 21 adhesion defective mutants and we used this information to construct ‘The S. aureus Genetic Adhesion Network’. Importantly, we identified a core gene set involved in adhesion to all three host ligands and we delineated unique genetic signatures. In addition, we demonstrate a central requirement for autolysin-mediated daughter cell separation in S. aureus CWA protein-mediated adhesion to host ligands, which contributes to virulence in murine skin and soft tissue infection. This comprehensive study will inform strategies to inhibit S. aureus host cell adhesion, potentially enabling the development of anti-adhesive therapeutics to complement traditional antibacterial chemotherapy.

2023-03-04 | PXD018514 | Pride

Genome-scale analysis of Staphylococcus aureus reveals host-specific diversification of the core genome.

Project description:Staphylococcus aureus causes disease in humans and a wide array of animals. Of note, S. aureus mastitis of ruminants, including cows, sheep and goats, results in major economic losses worldwide. Extensive variation in genome content exists among S. aureus pathogenic clones. However, the genomic variation among S. aureus strains infecting different animal species has not been well examined. To investigate variation in the genome content of human and ruminant S. aureus we carried out whole genome PCR scanning (WGPS), comparative genomic hybridizations (CGH), and directed DNA sequence analysis of strains of human, bovine, ovine, and caprine origin. Extensive variation in genome content was discovered including host- and ruminant-specific genetic loci. Ovine and caprine strains were genetically allied whereas bovine strains were heterogenous in gene content. As expected, mobile genetic elements such as pathogenicity islands and bacteriophages contributed to the variation in genome content between strains. However, remarkably, most host-specific differences were restricted to regions of the conserved core genome, which contained allelic variation in genes encoding proteins of known and unknown function. Many of these proteins are predicted to be exported and could play a role in host-pathogen interactions. These data suggest that diversification of the core genome may be more important than acquisition of novel genes for S. aureus host-adaptation. The host-specific determinants identified by the whole-genome approaches adopted in the current study represent excellent targets for studies of the evolution and molecular basis of S. aureus host specificity. Keywords: Strain vs strain eleven strains of Sa were compared at the DNA level in triplicate.

2008-11-18 | E-GEOD-10187 | biostudies-arrayexpress

Genome-scale analysis of Staphylococcus aureus reveals host-specific diversification of the core genome.

2008-11-19 | GSE10187 | GEO

Neutrophil gene expression in response to Mycobacterium abscessus

Project description:The response of human neutrophils to the emerging pathogen Mycobacterium abscessus has not been described. However, M. abscessus infections are frequently associated with neutrophil-rich abscesses. To better understand the reponse of neutrophils to M. abscessus we performed gene expression analysis using Affymetrix HG-U133A Plus 2.0 microarrays. Human neutrophils from healthy donors were stimulated with isogenic rough and smooth morphotypes of M. abscessus. Staphylococcus aureus was used as a control. Gene expression was compared to neutrophils left unstimulated. Neutrophils from four individual donors were isolated on separate days and stimulated with freshly prepared bacteria. Neutrophils (stimulated and control) were left for 2 hours before total RNA was isolated, and biotinylated cRNA was prepared by standard methods. Analysis indicates that M. abscessus morphotypes induce a limited number of genes, when compared to S. aureus, which are enriched in genes for cytokines and chemokines, including neutrophil-specific chemokines. These data suggest that neutrophils have a limited response to M. abscessus, which may contribute to neutrophil-rich abscess formation.!Series_overall_design = Human neutrophils from healthy donors were exposed to rough Mab (ATCC 19977T), smooth Mab (ATCC 19977T) and S. aureus (CF clinical strain) for two hours; control cells were exposed to saline.

2013-01-10 | GSE39889 | GEO

Global changes in Staphylococcus aureus gene expression in human blood provide insight into mechanisms of immune evasion and virulence

Project description:Staphylococcus aureus is a leading cause of bloodstream infections worldwide. In the United States, many of these infections are caused by a strain known as USA300. Although progress has been made, our understanding of the S. aureus molecules that promote bacteremia and survival in human blood is incomplete. To that end, we analyzed the USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB), a standard laboratory culture media. Notably, genes encoding several cytolytic toxins were up-regulated in human blood over time, and hlgA, hlgB, and hlgC (encoding gamma-hemolysin subunits HlgA, HlgB, and HlgC) were among the most highly up-regulated genes at all time points. Culture supernatants derived from a USA300 isogenic hlgABC-deletion strain (LAC?hlgABC) had significantly reduced capacity to form pores in human neutrophils and ultimately cause neutrophil lysis. Compared with the wild-type USA300 strain (LAC), LAC?hlgABC had modestly reduced ability to cause mortality in a mouse bacteremia model. On the other hand, wild-type and LAC?hlgABC strains caused virtually identical disease in a mouse skin infection model, and bacterial survival and neutrophil lysis after phagocytosis in vitro was similar between these strains. Comparison of the cytolytic capacity of culture supernatants from wild-type and isogenic deletion strains lacking hlgABC, lukS/F-PV (encoding PVL), and/or lukDE revealed significant functional redundancy among two-component leukotoxins in vitro. These findings may explain in part the apparent limited contribution of any single two-component leukotoxin to USA300 immune evasion and virulence. S. aureus strain USA300 transcriptome during culture in human blood, human serum, and trypticase soy broth (TSB): time course.

2011-08-25 | E-GEOD-25454 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data