The Vital Roles of Low Molecular Weight Thiols in Francisella tularensis

Author(s): Alexander Marchesani

Mentor(s): Monique van Hoek, School of Systems Biology

Abstract

Francisella tularensis is the bacterium which causes the disease tularemia or “rabbit fever” which effects hunters in the US and Eastern Europe. Because the pathogen is highly infectious, there is serious concern in the scientific community about tularemia being made into a bioweapon. My project was to study a class of molecaules called low molecular weight thiols (LMW thiols) and their many uses inside Francisella. LMW thiols are small amino acids which every living organism uses. Primarily, LMW thiols protect proteins and destroy certain toxins when the cell is under attack. However, bacteria such as E. coli have found many other uses for LMW thiols. There are two LMW thiols in Francisella which are called glutathione (GSH) and thioredoxin. My mentor, Dr. Monique van Hoek, and I set a goal to form a full literature review about the current knowledge of LMW thiols in Francisella. Additionally, we wanted to look for unanswered questions and future directions for the field. Interestingly, researchers that removed genes related to GSH and thioredoxin noticed that the infection by Francisella often grew weaker. Further studying mutants like this could help identify candidate genes to make a vaccine for the disease. Additionally, glutathione may contribute to the highly important process of creating DNA. Glutathione and thioredoxin have a wide range of abilities inside of Francisella and better understanding them can aid in dealing with this potential bioweapon.

Video Transcript

Hello, my name is Alexander Marchesani and my project is about the functions of low molecular weight thiols to deal with stress and growth in the bacteria Francisella tularensis. Before we begin, I want to thank my mentor, Dr. Monique van Hoek, for being constantly in contact with me and working closely during the process of editing and refining our work.

The bacteria Francisella tularensis was the focus for my project. This is a bacterium that causes a disease known as tularemia and has a few unusual characteristics. Firstly, Francisella can infect a huge variety of animals including humans, insects, deer, and rabbits. In fact, the nickname for tularemia is “rabbit fever” and it infects hunters in the US and Eastern Europe. Another interesting aspect of Francisella is that it can infect humans extremely easily. For example, some studies have shown that as few as 10 cells can infect someone if inhaled. To put that into perspective, that’s around 1000x more infectious than anthrax. However, rabbit fever is surprisingly uncommon with only around 100 cases yearly in the US. Now you may be asking, if its no big deal, why are we interested in it? Well, because Francisella is highly infectious and can cause disease when inhaled, that gives it perfect potential to be weaponized. The Soviet Union successfully weaponized tularemia during the Cold War. Fortunately, it was never actually used. My research project focused on creating a literature review about the role of low molecular weight thiols inside Francisella.

Low molecular weight thiols are essentially small amino acids and proteins that can do a huge variety of things. For example, the molecule called glutathione can help neutralize toxins our bodies use to stop infections like nitric oxide and hydrogen peroxide. Additionally, Francisella can steal the glutathione present inside human cells. This stolen material can then be broken down to help the infection grow and spread. Glutathione is the major low molecular weight thiol in Francisella. However, several other molecules also assist in these processes. One example is a protein called thioredoxin. Thioredoxin, along with glutathione, can help shield vulnerable cellular machinery when Francisella is under attack. When genes related to thioredoxin and glutathione are removed, Francisella is less able to grow and cause disease in mice and human cells. This indicates that our molecules are crucial in fending off the attack from the bodies immune system. Better understanding how glutathione and thioredoxin function in Francisella could help vaccination efforts already ongoing.

By now you may be asking yourself, “this is all well and good but what did you actually do?”. Conveniently enough, I am about to explain that very thing! I started this project with OSCAR in the summer and spent much of that time reading sources and learning as much as I could about my subject. This semester, I have been working closely with my mentor to finalize a literature review which examines everything I have already talked about and more. This will incorporate dozens of different experiments on the subject from other labs. Additionally, we have a bit of data about our genes from before COVID hit which helps illustrate our results. Currently, we have about 12 pages of material and we are ironing out a few more details before we submit to a journal for publication. We expect to be done before the end of the year and I will continue this project even after my grant at OSCAR is officially over.

I wanted to say how grateful to the OSCAR office and Dr. Karen Lee for finding a way to make things work online and for keeping the students in contact through various exercises and meetings. This project has taught me how to write and organize a scientific article and analyze highly technical sources. This kind of familiarity is invaluable for graduate programs and a career in science as a whole. Thank you for listening and I hope I was able to teach you a little something about the tiny creatures which impact our lives so much.

4 replies on “The Vital Roles of Low Molecular Weight Thiols in Francisella tularensis”

Well done, Alexander. I enjoyed the use of humor and also learning something about Tularemia and LMW Thiols. Does knowing more about how Thiols work in the bacteria allow us to prevent its use a a bioweapon to to make it easier to treat if people are infected in the more typical ways?

Hello Dr. Lee,

Right now, there is not much we could do to prevent tularemia from being weaponized. If the resources and time were used, it could happen. The current push is to develop a vaccine or some other treatment(s) to be able to deal with an attack should it happen.

Understanding thiols in Francisella could help identify genes for vaccine targets (or some other kind of treatment). For example, removal of genes related to the synthesis of the thioredoxin protein causes Francisella to grow and spread significantly less inside mice

Hi Alexander, this was a very informative presentation! You mentioned that you have some data regarding COVID. I was wondering if you have researched the role of thioredoxin and glutathione win regards to COVID and their immunity against COVID, since COVID can also be caused when inhaled?

Leave a Reply