Deciphering Staphylococcus aureus-host dynamics using dual activity-based protein profiling of ATP-interacting...

Area of Science:

• Microbiology
• Cell Biology
• Immunology

Background:

• Adenosine triphosphate (ATP) is crucial for cellular processes, including host-pathogen interactions and immune responses.
• Staphylococcus aureus (S. aureus) infection involves complex dynamics between the bacteria and host cells, necessitating a deeper understanding of cellular adaptations.

Purpose of the Study:

• To investigate the ATP-interacting proteins in S. aureus and human cell lines (macrophages THP-1 and keratinocytes HaCaT) during intracellular infection.
• To dissect the dynamic proteomic interactions and cell-type-specific responses during S. aureus infection.
• To identify bacterial strategies for persistence and host modulation within different cell types.

Main Methods:

• Utilized a chemoproteomic approach with a desthiobiotin-ATP probe to profile active ATP-binding proteins.
• Analyzed protein activity and pathway enrichment in S. aureus within THP-1 and HaCaT cells.
• Mapped differentially activated proteins to biochemical pathways in host cells to understand cell-type-specific adaptations.

Main Results:

• S. aureus upregulated pathways for nutrient acquisition, amino acid metabolism, and energy metabolism within human cells.
• Distinct bacterial adaptations were observed in macrophages (THP-1) and keratinocytes (HaCaT).
• THP-1 cells prioritized immune defense, inflammation, and autophagic cell death, while HaCaT cells focused on barrier integrity and immune activation.

Conclusions:

• S. aureus exhibits tailored adaptations to intracellular environments of macrophages and keratinocytes.
• Host cells mount distinct defense strategies against S. aureus, involving metabolic reprogramming and immune pathway activation.
• Findings provide insights for developing immunomodulatory therapies targeting S. aureus infections.