Antibiotic filament enzymes assemble into larger structures, locking onto the surface of bacterial cells like Velcro sticking together. Image Source: Nature Microbiology
Researchers from Utrecht University in the Netherlands have discovered that a small molecule antibiotic called filastatin can assemble into larger structures, locking onto the surface of bacterial cells like Velcro, preventing the bacteria from escaping and continuing to infect body cells. The related paper was published in the latest issue of Nature Microbiology, holding significant importance in the development of novel antibiotics to combat drug-resistant bacteria.
Using advanced techniques such as solid-state nuclear magnetic resonance and atomic force microscopy, the researchers delved into the working mechanism of filastatin.
Traditionally, antibiotics act by targeting specific molecules within bacterial cells. Filastatin is an antibiotic derived from fungi, and until now, the mechanism behind its effectiveness has remained unclear.
Previous studies suggested that the key was filastatin binding to a molecule called lipid II (crucial for synthesizing bacterial cell walls), akin to a key fitting into a lock.
The new research revealed a more intricate process: filastatin not only acts as a key but also forms dense structures on the bacterial membrane containing lipid II. These supramolecular complexes act like tiny "hooks" attached to the bacterial "loop," capturing the target lipid II and preventing its escape. Even if one lipid II breaks free from a "hook," the bacteria remain trapped among numerous "hooks," unable to escape and cause further infection.
Furthermore, calcium ions in filastatin can further enhance its antibacterial activity. These ions coordinate with specific regions of the filament enzyme, inducing structural changes that significantly boost its antibacterial effects.
The researchers noted that this discovery fills a significant knowledge gap and holds crucial importance in designing better drugs to combat the growing threat of antibiotic resistance.
