Crotonylation driving Streptococcus pneumoniae adaption and virulence

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Drug-resistant bacteria often reduce virulence to survive host defenses.
• Protein post-translational modifications (PTMs) are critical but their role in bacterial virulence is not well understood.

Purpose of the Study:

• To investigate the role of lysine crotonylation (Kcr) in Streptococcus pneumoniae virulence and survival.
• To elucidate the mechanism by which Kcr affects bacterial adaptation.

Main Methods:

• Quantitative proteomics and animal models were used to study Kcr in multidrug-resistant S. pneumoniae.
• A crotonyltransferase (SPD_0839) was identified and characterized using multi-omics approaches.
• Antibody-based enrichment and biochemical assays were employed to map enzyme-substrate interactions and analyze pneumolysin (PLY) modulation.

Main Results:

• Kcr regulates bacterial virulence and host adaptation in S. pneumoniae.
• SPD_0839 acts as a crotonyltransferase, modifying 153 substrates and impacting energy metabolism.
• Kcr modification of PLY by SPD_0839 enhances its pore-forming activity, increasing bacterial hemolysis and virulence.

Conclusions:

• Lysine crotonylation is a key regulator of pneumolysin activity and bacterial virulence in S. pneumoniae.
• This research provides insights into Kcr's role in bacterial survival and suggests potential targets for new antibacterial drugs.