A zinc-dependent adhesion module is responsible for intercellular adhesion in staphylococcal biofilms

Area of Science:

• Microbiology
• Biochemistry
• Structural Biology

Background:

• Hospital-acquired bacterial infections pose significant global health risks.
• Staphylococcal species, particularly Staphylococcus epidermidis and Staphylococcus aureus, are major contributors to these infections.
• Bacterial biofilm formation by staphylococci complicates treatment and increases morbidity and mortality.

Purpose of the Study:

• To elucidate the precise role of cell-surface protein G5 domains in staphylococcal biofilm formation.
• To investigate the structural and functional properties of G5 domains in adhesion.
• To explore potential therapeutic strategies targeting staphylococcal biofilm development.

Main Methods:

• Analytical ultracentrifugation (AUC) to study G5 domain dimerization.
• Circular dichroism (CD) to analyze G5 domain structure.
• Biofilm plate assays to assess the impact of zinc chelation and soluble G5 domains on biofilm formation.

Main Results:

• G5 domains function as zinc (Zn(2+))-dependent adhesion modules, analogous to mammalian cadherins.
• Zn(2+) binding induces G5 domain dimerization, mediated by 2-3 Zn(2+) ions at the dimer interface.
• Tandem G5 domains associate modularly, suggesting a 'zinc zipper' mechanism for intercellular adhesion.
• Zinc chelation specifically inhibits biofilm formation in Staphylococcus epidermidis and methicillin-resistant Staphylococcus aureus (MRSA).
• Soluble G5 domains inhibit biofilm formation in a dose-dependent manner.

Conclusions:

• Staphylococcal biofilm architecture arises from the self-association of G5 protein domains.
• The identified zinc-dependent mechanism of intercellular adhesion may be conserved across staphylococci and other Gram-positive bacteria.
• Zinc chelation presents a promising therapeutic strategy for combating diverse bacterial biofilm-related infections.