How are we fighting antibiotic-resistant superbugs?
In Dr. Mario Rivera’s lab, an undergrad works on the frontlines in the war against diseases.
Emily Cambre is not your ordinary 20-year-old LSU student. The junior undergraduate balances her time between studying the microscopic world of bacterium and the human psyche as a double major in chemistry and psychology. Emily has spent the past several months as part of the Rivera Research Group, working in LSU chemistry professor Mario Rivera’s lab. In the lab, the team is trying to synthesize a novel treatment to combat bacteria such as Pseudomonas aeruginosa. This particular bacteria is known for its ability to rapidly develop resistance to multiple classes of antibiotics — an ability they are dealing with in the lab currently.
Dr. Mario Rivera’s research program is focused on:
“understanding iron homeostasis in bacteria with the long term goal of validating bacterial iron homeostasis as a potential target for antibiotic development. Bacterial iron homeostasis offers a significant vulnerability because: (i) essential iron must be obtained from the host, (ii) the concentration of free iron in the host is vanishingly low, (iii) in the bacterial cell iron can be toxic and must be stringently regulated, and (iv) Iron homeostasis endows the bacterial cell with the ability to sense intracellular and environmental iron levels, and mount coordinated responses to procure iron, or to defend from potential iron-induced toxicity.”
We had the opportunity to talk to Emily Cambre, and during our conversation about her research, we also learned a lot about her as a person and what motivates her to strive for more.
CoS: What has it been like working in a lab on such serious science projects as an undergraduate?
Emily: A typical day in the lab starts at 11:30 a.m. for me. I come in and get it all ready. The person I’m paired with right now is named Achala. She’s a graduate assistant. She’s amazing. We work together to perform some of the techniques in order to analyze the different bacteria we’re studying in the lab. I’m currently working on a gel electrophoresis, which is just like studying the protein as it’s unfolded, and staining it to see which proteins are there.
Currently what we’re looking at is a bacterioferritin, which is called BfrB. This is basically a storage unit within the bacteria. It stores iron, which is vital to cell growth and homeostasis.
(Homeostasis is the state of steady internal conditions maintained by living things. This dynamic state of equilibrium is the condition of optimal functioning for the organism.)
But some of the different forms of iron can not only be limiting in bio-availability, but it can also be toxic. So, that storage unit is actually very crucial in order to maintain the health of the bacteria. In order for that storage unit to release iron, it has to have a protein-protein interaction with a ferredoxin, and that is a Bfd. Basically, when the BfrB and the Bfd interact iron can be released from the storage unit and assist the bacteria in its growth. We’ve actually inhibited that interaction already. The binding site where the Bfd activates with the BfrB has been blocked so that Bfd cannot make contact with that BfrB anymore. The iron storage can’t be released into the bacteria.
We’ve seen that, in comparison between the natural wild type and the mutant that we’ve created, the growth has been substantially decreased. But there is almost like a back-up plan that the bacteria has, where it secretes these molecules of pyochelin and pyoverdin and those attract iron from the environment and bring it back into the bacteria.
Pyochelin and pyoverdine are both siderophores. Those are the molecules that bind and transport iron from the environment into the bacteria. Visually you’ll see in a really iron-depleted environment with the bacteria in it, the flask will have this liquid in it that’s super fluorescent yellow and greenish colors. It’s very obvious that the siderophores have been secreted and it’s pulling as much iron from the media into the bacteria (as it can.)
That’s where further research is heading toward. It’s understanding these fluorescent molecules and how we can stop that secretion, as well as understanding how it’s activated and how we can get around that. With what’s being studied right now, we’re trying to understand the mechanisms and interactions that go on with the environment and the bacteria and how the bacteria is reacting.
CoS: You’ve said this is your first semester researching in a lab. Have you had any other interesting and exciting experiences?
Emily: I’ve done experiments as outreach. We went to a school and were introducing all kinds of chemistry concepts to Boy Scouts. That was the scariest thing because it was around 40 little boys running around, dipping their hands in liquid nitrogen and are like “oh my god, it hurts!” I’m like, “Yes. Take your hands out of it!” At the end, we dump the rest of the liquid nitrogen on the floor and create that really cool smoke effect. They all wanted to run into the liquid nitrogen as we’re pouring it. Editor’s note: No boy scouts were harmed in the making of that story.
CoS: Did you have support for your scientific interests early on from family, friends or teachers?
Emily: My interest in science began with the fact that I had amazing teachers growing up — one teacher being my dad. Just all the different road trips we went on, he would randomly tell me everything about some place or object we passed. Since middle school, I’ve consistently had really good, supportive science teachers who brought the best out of me. It was one of the few subjects I felt challenged in, and that was exciting.
I find that the teachers who have those wild moments or those crazy stories, those are the lectures you remember the most. It definitely saves time studying when you remember those instances.
CoS: Even though you’re new to research, you mentioned you’d received a science scholarship.
Emily: I’m a Patrick Taylor Chemistry Award recipient. It’s an award that acknowledges your potential as a student to go above and beyond in your field. It was awarded to me not only by Mrs. Taylor but also the faculty in the chemistry department. I remember going to Dr. Linda Allen and being like, “Where did all this money come from? Do I have to give it back?” She explained about the award and that they hadn’t yet emailed me notification that I’d won an award. It's cool, I liked it a lot.
CoS: You have an interesting combination of majors. What were your reasons for choosing to pursue psychology as a second major?
Emily: My dad has bipolar disorder. Growing up with that, it was a different family household. He was diagnosed when I was 15. Growing up wasn’t real easy for me, especially my relationship with my dad, but I try to be as close with him as possible and make sure he’s doing his treatments like he’s supposed to. The big thing with bipolar disorder is a lot of people resist taking their treatment because it stops the manic episodes. That seems to be one of the things they need.
It’s one of those things where… if I could help one person, I’d want it to be my family. I wouldn’t be the person I am, or even be in college, if it weren’t for my dad. He really stressed the importance of education to me. I’m the youngest of four, and I’m the only one who is going to go to college and get a degree. So… thanks dad!
What I plan to do with my degree is work in a lab. I like the research and development aspect of everything. I would really like to work on the synthesis of a new drug, specifically anti-psychotics. I’m really interested in schizophrenia. There’s not a lot of research done on it. We don’t have a really good grasp of it just yet.
CoS: How has your family reacted towards your achievements at LSU?
I always go to my mom and tell her everything that’s going to happen in the week and everything that I’m receiving, like awards, and getting the opportunity to work under Dr. Rivera. I was really excited. She was like, “Mmhmm.” She’s really happy for me, but when I’m explaining to her what exactly I’m studying, it’s kind of a glazed-over (look). That’s like my brothers. They’re really excited, but, more-so my dad is really excited. I think, growing up they were like, “You’re going to do great things.”
I remember in eighth grade, I wanted to be a cardiologist. Everybody else was like, “I want to be a nurse.” But no, I wanted to be a surgeon.
CoS: Any words of wisdom?
Emily: I’m a first-generation college student. My parents didn’t go to college. You can start wherever you are. You don’t have to come from a certain background. You can just have a passion for something and push toward reaching your goal. There are a lot of barriers I had to go through in order to get here. Especially with this school (LSU), there are people here to help you. Just find something you’re interested in and move toward it.
In case you didn’t know…
Bfd is a new type of [2Fe-2S] protein whose function contributes to the iron homeostasis machinery in P. aeruginosa3 (see below) by enabling the mobilization of iron from BfrB. In the absence of Bfd or when the BfrB:Bfd interaction is blocked, iron in BfrB irreversibly accumulates in P. aeruginosa cells, which causes iron deficiency in the cytosol. Hence, blocking the BfrB:Bfd interaction is probably a viable approach to hijacking iron homeostasis in P. aeruginosa and probably in many other bacteria. (https://pubs.acs.org/doi/pdf/10.1021/acs.biochem.8b00823)
Pseudomonas aeruginosa is a common gram-negative, rod-shaped bacterium that can cause disease in plants and animals, including humans. P. aeruginosa is a multidrug resistant pathogen recognized for its intrinsically advanced antibiotic resistance mechanisms, and its association with serious illnesses – hospital-acquired infections such as ventilator-associated pneumonia and various sepsis syndromes. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772362/)