Metabolic glycoengineering of Staphylococcus aureus reduces its adherence to human T24 bladder carcinoma cells

Area of Science:

• Microbiology
• Biochemistry
• Infectious Diseases

Background:

• Staphylococcus aureus is a major human pathogen causing severe infections, particularly in healthcare settings.
• The rise of antibiotic-resistant strains, like community-acquired methicillin-resistant S. aureus (CA-MRSA), poses a significant global health threat.

Purpose of the Study:

• To apply metabolic glycoengineering to Staphylococcus aureus for the first time.
• To investigate the potential of bioorthogonal click chemistry to modify and study S. aureus.
• To assess the impact of these modifications on bacterial adherence to human cells.

Main Methods:

• Metabolic glycoengineering using N-azidoacetyl-glucosamine (GlcNAz) was performed on S. aureus.
• Bioorthogonal Cu(I)-catalyzed azide-alkyne Huisgen cycloaddition (CuAAC) click reaction was employed to link alkyne dyes to the modified bacteria.
• Bacterial adherence assays were conducted using human T24 bladder carcinoma cells.

Main Results:

• Metabolic glycoengineering with GlcNAz was successfully achieved in S. aureus.
• Azido-functionalized S. aureus cells could be effectively stained using alkyne dyes via click chemistry.
• Bacterial adherence to T24 bladder carcinoma cells was reduced by 48% after metabolic glycoengineering and staining.

Conclusions:

• Metabolic glycoengineering is a viable approach for functionalizing S. aureus.
• Bioorthogonal click chemistry provides a powerful tool for visualizing and potentially manipulating S. aureus.
• The observed reduction in bacterial adherence suggests therapeutic potential for glycoengineered S. aureus strains.