Atomic structures of a bacteriocin targeting Gram-positive bacteria

Area of Science:

• Structural biology
• Molecular microbiology
• Biophysics

Background:

• Bactericidal contractile nanomachines are promising antibiotic candidates, but their engineering requires atomic-level structural understanding.
• Existing nanomachines target Gram-negative bacteria, leaving a gap for Gram-positive pathogen treatment.
• Differences in bacterial envelopes necessitate distinct machine designs for effective targeting.

Approach:

• Determined atomic structures of an engineered diffocin targeting the Gram-positive bacterium Clostridioides difficile.
• Captured structures in pre-contraction and post-contraction states to elucidate mechanism.
• Analyzed protein components including the baseplate, trunk, collar, hub-hydrolase, and tape measure protein.

Key Points:

• Reported atomic structures of a diffocin, a contractile syringe-like machine targeting Gram-positive bacteria.
• Identified significant differences in the baseplate and contraction magnitude compared to machines targeting Gram-negative bacteria.
• Revealed the role of the hub-hydrolase protein in peptidoglycan degradation and the structure of the tape measure protein.

Conclusions:

• The study provides mechanical insights into diffocin function and bacterial envelope interactions.
• Findings offer principles for designing potent, precision protein-based antibiotics against Gram-positive bacteria.
• Paves the way for developing novel antimicrobial strategies targeting specific bacterial pathogens.