mCherry cells
MR2-The wolf in the sheepfold: how S. aureus penetrates host cells...
UMR STLO Unit
RESEARCH
Microbio group
MR2-The wolf in the sheepfold: how S. aureus penetrates host cells...

The wolf in the sheepfold: how S. aureus penetrates host cells...

Staphylococcus aureus, an opportunistic pathogen, causes a wide range of illnesses, from benign skin infections to potentially fatal food poisoning. It is also one of the main bacteria responsible for nosocomial infections in France. Initially thought to be extracellular, S. aureus has recently been detected inside various cell types of infected hosts. Identifying the biological processes involved in the cellular response to S. aureus is necessary to understand the mechanisms of chronic infection, and to develop methods of combating it.

The researchers have developed a long-term in vitro infection model, specifically isolating cells with internalized bacteria. This persistent infection model makes it possible to isolate only cells containing internalized S. aureus, in order to identify potential markers and understand the mechanisms of chronic infection. Thanks to this model, we were able to sequence the transcriptome of cells containing S. aureus at an unprecedented level of resolution, showing that:

  • Cellular immune and inflammatory responses are exacerbated.
  • Metabolic pathways favoring bacterial persistence are implicated.
  • Genes encoding epigenetic regulators, notably those of chromatin repressor complexes and epifactors involved in DNA methylation, are down-regulated.
  • New mechanisms, such as the neuronal system pathway, the senescence pathway, or chromatin organization, have been identified using our model.

 

Metabolic pathways affectes by internalisation of Staphylococcus aureus
© Nadia Berkova

 

Conclusion: The knowledge gained from the persistent infection model improves our understanding of the biological processes involved in chronic S. aureus infections. It also guides future research and identifies candidates for the development of diagnostic, prophylactic and therapeutic approaches. Deregulation of epigenetic and DNA repair pathways suggests that long-term intracellular S. aureus infection impacts the host cell genome and epigenome, leading to pathophysiological dysfunctions in addition to the immune response during the infection process.

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Modification date: 12 January 2024 | Publication date: 10 January 2024 | By: STLO