Microcin B17, an antibiotic that kills E. coli bacteria. Before activating, the antibiotic embedded in a structure called a prodrug, like the core of an unsharpened “molecular pencil.”
Now, scientists at Rutgers University-New Brunswick and others discovered a “molecular pencil sharpener” that chews away its outer coating to release the powerful antibiotic. This discovery opens the door to finding new antibacterial agents and drugs to fight toxins. The scientists studied TldD and TldE bacterial proteins involved in making microcin B17.
“We think this may be a gizmo that bacteria use to activate processes which are dormant until the moment is right, when the pencil sharpener gets turned on and releases antibiotics,” said, Konstantin Severinov, senior author of a new study.
Many bacterial cells make inactive compounds called prodrugs, precursors that turn into drugs in the body. It’s like a future drug and when the need arises the drug is activated and it’s like a toxic warhead that gets exported outside the cell and kills its harmful neighbors.
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Severinov said, the prodrug examined by the scientists like a stick with two parts. The core part is the toxic warhead. A “leader” is on the other end and prevents the warhead from functioning until the right time.
Tld genes are common in bacteria. The study suggests that they play an important function in bacterial physiology. The Tld genes control protein quality and activating different natural products including antibiotics, such as microcin B17.
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Severinov said, every bacterial genome sequenced to date has Tld genes. Nobody knew what they do, and now we know what they do in one case, and we think that similar functions activate the production of bio-active compounds used by other bacteria as antibiotics or toxins.
Some toxins could use in a beneficial way. For example, people using bacterial toxins to kill insects for decades. When bacteria produce toxins that harm humans, drugs that inhibit Tld and fight such bacteria could develop.
However, the findings could lead to future applications in the protein engineering and synthetic biology fields.
More information: [Structure]