Research
β-lactam antibiotics, such as penicillin, have been important for treating bacterial infections. However, the prevalence of antibiotic resistance has increased over time. Understanding how bacteria adapt to and overcome antibiotics is imperative for the future treatment of antibiotic resistant infections. In Bacillus cereus, anthracis, and thuringiensis, β-lactam resistance is conferred by β-lactamases and penicillin binding proteins. These proteins either directly degrade β-lactam antibiotics or modify the target of β-lactams so they can no longer bind and kill the bacteria, respectively. These proteins are not produced unless they are needed. To produce these proteins bacteria have developed mechanisms to sense the presence of β-lactams and activate transcription of β-lactamases and PBPs.
In Bacillus cereus, anthracis, and thuringiensis the transcription of β-lactamases and PBPs is controlled by σP. σP belongs to a group of transcription factors called extracytoplasmic function (ECF) σ factors. ECF σ factors are inhibited in the absence of stress and are activated in the presence of stress. The anti-σ factor RsiP inhibits σP in the absence of β-lactam antibiotics. We have found the PBP, PbpP, senses the presence of β-lactams which causes RsiP to be sequentially degraded by two proteases: SipP and RasP. This results in the activation of σP and subsequent transcription of β-lactamases and PBPs, which neutralize the threat of β-lactams. Future work aims to determine how the components in the σP signaling system work together to activate β-lactam resistance. Specifically, we predict PbpP interacts with another protein involved in σP activation. We hope to identify this protein and define this interaction.
About Kelsie
Kelsie was born in Rockford, Michigan as the second child of Judy and Lawrence Nauta. As the offspring of veterinarians, she and her three siblings grew up admiring an abundance of bugs, frogs, turtles, and cats, as well as various other animals. She graduated from Rockford High School in 2012.
Kelsie earned a Bachelor of Science in Biology from the Fredrick Meijer Honors College at Grand Valley State University in Allendale, MI. During this time, she joined the laboratory of Dr. Matthew Hart. Here, she worked on microwave assisted catalytic hydrogenation for the synthesis of diphenyl urea derivatives and determined the minimum inhibitory concentrations of the newly synthesized compounds for E. coli and S. aureus. For her senior honors thesis, she joined the laboratory of Dr. Steven Hecht and worked to develop a model system for the discovery of Bacillus cereus bacteriophages that could rescue Galleria mellonella from infection. These experiences imparted an appreciation for the scientific process and excitement for potential novel discoveries.
In 2016, Kelsie moved to Iowa City to attend graduate school at the University of Iowa. She joined the laboratory of Dr. Craig Ellermeier in the spring of 2017. For her thesis work, she studied the control of the transcription factor σP, which regulates the expression of β-lactam antibiotic resistance. This work has culminated in a complete working model for the control of σP activation. Her favorite part was the discovery of a point mutation that renders Bacillus anthracis, the causative agent of anthrax, sensitive to penicillin. After graduation, Kelsie plans to join the laboratory of Dr. Erin Carlson at the University of Minnesota as a post doc, where she will continue to study bacterial signal transduction in various bacterial species.
Outside of the lab, Kelsie enjoys spending time with her friends, family, and partner, Evan. She has gone on many hiking, swimming, or kayaking adventures with friends and fellow graduate students. She also has spent much of her free time rock climbing at the CRWC. If she has not dragged you to the climbing wall yet, it’s not too late! Kelsie also enjoys running around Iowa City with Nicki, Julian, and Vincent and discussing the ways of the human world with her cat, Molly.