A Molecular Pencil Sharpener

Picture this. A brand new, unsharpened pencil. The graphite in the center cannot be used to write until a pencil sharpener chews away at the wooden tip.

But in this case, the graphite resembles chemicals that can make a “warhead” toxic once it’s sharpened by bacterial proteins. The proteins will remain inactive until the “leader” -- the wood surrounding the pencil -- is removed. The pencil sharpener itself is the bacterial protein, Tld. The shavings in the pencil sharpener are the remains of the leader being chopped up by the proteins, which releases a powerful antibiotic that can kill E. coli­.

Scientists at Rutgers University have discovered what they call a molecular pencil sharpener that can chew away the outer coating of microcin B17 to release this powerful antibiotic.  This discovery opened numerous doors to finding new antibacterial agents and drugs to fight toxins.

Many bacterial cells make inactive compounds that are called prodrugs. These are precursors that turn into drugs in the body. So, it’s like a future drug that is activated or released when the going gets tough. It’s just like the saying, when the going gets tough, the tough get going. When the drug is activated, the toxic warhead gets exported out of the cell and kills any harmful neighbors.

The TldD protein has a hole in it, just like a pencil sharpener, where the prodrug can be fed into. The sharpener chews on the leader, which activates the toxic warhead, kicking it out of the cell. This is almost like having the ability to produce toxic compounds, including antibiotics, a la carte whenever you need them.

Ghilarov, D., Serebryakova, M., Stevenson, C. E., Hearnshaw, S. J., Volkov, D., Maxwell, A., ... & Severinov, K. (2017). The Origins of Specificity in the Microcin-Processing Protease TldD/E. Structure.