I am in a room full of keys made of poison (don’t ask why). I grab one poisonous key to open a very specific door, causing me to let go of the slightly different non-poisonous key that has the job of adding an extra lock to the same specific door. This door leads to the tools needed to get rid of the other poisonous keys in the room by producing two tools. One can capture the poisonous key from my hand (or anywhere in the room) and hand it off to tool two, which throw it away out of the room. This continues until all of the poisonous keys are gone or at a low enough amount that I won’t succumb to the poison. The first tool also makes a tiny modification to the poisonous key in order to put said key through the slot of the second tool that gets rid of it. Keeping the door open for no reason is a bad thing (like the fridge door), hence having the non-poisonous key is good to have around which is what I had to let go to grab the poisonous key to open the door. Hence, too much of that non-poisonous key would prevent me from responding well or grab to the poisonous key…But what does it all mean?!?!?
It occurred to me that I wrote a scientific article and didn’t exactly say what I think it means to the field or to people that aren’t in the field. I’d like to take this time to correct that. In October of last year, I published my first senior author research article at the University of Arizona. It was entitled “Copper Chaperone CupA and Zinc Control CopY Regulation of the Pneumococcal cop Operon” in a journal called mSphere, and open access journal through the American Society of Microbiology. Now, before you run away screaming, let me try to explain what all that is. If you only partially understood the first paragraph, then you are in good shape.
Ok let me start by the obligatory, copper is toxic to a variety of bacteria, including Streptococcus pneumoniae or pneumococcus (yes, the one there is a vaccine for) and other potentially antibiotic resistant bacteria. We think understanding how copper kills bacteria is important to know so we can figure out how to make copper work better. We also want to know how the bacteria tries to fight back against the copper stress. We know somethings, like they have specialized systems for kicking out copper and these systems could be drug targets.
S. pneumoniae has a copper export system, or the cop operon, to export copper (the poisonous key) that consist of an export protein (this exports the copper or the second tool listed above), a chaperone (this guides copper to the exporter for export and is CupA listed in the title, the first tool), and a repressor (this protein makes sure that the bacteria doesn’t make a bunch of proteins it doesn’t need, it, CopY, stops the cop operon from being on until it, see copper, then it releases the DNA so all three proteins can eventually be made aka, me in the story above). Zinc is the non-poisonous key listed. DNA is the door.
The article (which hopefully matches with the story above):
1. I mentioned that copper makes the CopY repression release the DNA, but zinc actually makes the protein clamp down on the DNA. These metals are right by each other on the periodic table so that is quite the effect. We didn’t know that happened with a metal export system before. Adding zinc with copper prevented the repressor from “opening the door” to the operon thus have the effect of killing the bacteria faster than just with copper alone. Copper and zinc make brass so this is known as my super hero name, the Brass Dagger.
2. If you look at the picture, copper II AKA Cu2+ AKA blue lighting (ok the last one is made up) comes into the bacteria, and copper I AKA Cu1+ AKA…well it’s brown like your pipes so…I got nothing…anyway. To get kicked out the cell, it has to be the 1+ version. That 2+ to 1+ is the gain of an electron, a negative charge hence the number going down. We believe that electron has to come from inside the bacteria somehow, but from what and from where? Well, we found that the chaperone (CupA) could give the copper an electron to make it go from Cu2+ to Cu1+. But where is that protein getting electrons from, stay tuned! Or better yet, why does it matter. Loosing electrons has to come at a cost to bacteria and we think trying to keep up with the copper reduction (that’s what adding an electron is called because you are reducing the charge from 2+ to 1+, like adding a negative number). This reduction ends up really harming the bacteria. This chaperone can also take the copper away from the repressor so that it can go back to “shutting the door.”
Hopefully the story above makes a bit more sense now in context.
Cool, can we exploit that? We think so, we hope so, but we need to keep digging. Anyway, that’s the paper. I hope you enjoyed this little review of my laboratory’s recent work. Happy to answer any questions.