Phuong Tran successfully defended her PhD thesis entitled, “Investigations into Staphylococcus aureus β-Toxin Pathogenesis” on Thursday, November 18. 2021. Phuong (left) is pictured with her mentor, Dr. Wilmara Salgado-Pabón, PhD (right).
Research
Staphylococcus aureus is the leading causative agent of infective endocarditis (IE) in high-income countries. IE is an infection of the cardiac endothelium characterized by “vegetative” lesions on the heart valves. If left untreated, staphylococcal IE has high morbidity and a 40-50% mortality rate. Evidence has shown β-toxin extensively contributes to potentiating IE. Functional studies into the mechanisms underlying β-toxin contribution to IE are limited. My work has focused on several aspects of β-toxin biology with the goal of identifying its relevant contributions to S. aureus pathogenesis.
β-toxin is an understudied toxin because most clinical isolates contain a phage inserted into the encoding gene, hlb, thereby inactivating its transcription. The relevance of β-toxin was debated, even though, when produced, it significantly contributes to disease severity. With evidence that the phage excises during infection, I investigated the relationship between hlb and its integrating phage. I found that phage excision events are differentially induced during biofilm growth and oxidative stress. I concluded that β-toxin expression is controlled by a phage-regulatory switch to be produced during conditions that S. aureus specifically encounters during infections. β-toxin is a relevant S. aureus virulence factor.
β-toxin’s enzymatic activity produces sphingolipid metabolites in eukaryotic cells. These are potent signaling molecules that regulate cell fate and angiogenesis (new vessel formation critical for tissue repair). I sought to investigate whether β-toxin modulates angiogenesis as a mechanism for IE pathogenesis, as S. aureus IE lesions are non-healing and tissue destructive. I showed that β-toxin inhibits wound healing from human aortic and human umbilical vein endothelial cells, and abolished sprout formation in a rabbit aorta explant model. To accomplish this, β-toxin prevents cell proliferation and migration. Thus, β-toxin contributes to overall IE pathogenesis by perturbing proper tissue repair. In summary, my work has demonstrated potential mechanisms by which S. aureus senses its environment and produces β-toxin to promote disease.
About Phuong
Phuong was born in Vietnam and soon after immigrated to the United States, where her family relocated to St. Cloud, Minnesota. The child of a machinist and manicurist, Phuong was the first in her family to attend a four-year college. She graduated with a Bachelor of Arts in Biology from St. Olaf College in 2012. By 7th grade, Phuong knew she wanted to work with pathogens. But it was during her time at St. Olaf, Phuong discovered she wanted a career where she could think about what makes pathogens so successful.
She next attended The University of Minnesota-Duluth, where she obtained a Master of Science in Integrated Biosciences with a Cellular, Molecular, and Physiology emphasis. Here she worked in the lab of John L. Dahl investigating nontuberculous Mycobacterium stress responses and antibiotic resistance. She discovered novel environmental Mycobacterium species that exhibited remarkable tolerance to low pH and low-temperature growth conditions. When she started in the lab, she was afraid to touch anything before asking, including clean glassware. She also messed up her first miniprep. By the end, the lab was her second home.
Afterward, Phuong became an Adjunct Instructor at Coe College in Cedar Rapids, Iowa. She was the sole course instructor for Introductory Microbiology in the spring of 2015. These were informative and enriching experiences for Phuong and solidified her academic career path. In the fall of 2015, Phuong joined the lab of Dr. Bradley Jones at the University of Iowa as a Research Assistant. She was part of a team spearheading new adventures into Streptococcus sanguinis virulence factors important in infective endocarditis. While working for Dr. Jones, Phuong returned to Coe College in the spring of 2016 to teach Topics in Evolution.
In the fall of 2016, Phuong joined the University of Iowa and ultimately entered the laboratory of Dr. Wilmara Salgado-Pabón. Phuong has had many wonderful opportunities to mentor an REU student and numerous undergraduate students, attend several regional conferences and present her work to her peers and mentors within the department. Phuong finished her PhD work at the University of Wisconsin-Madison, where Dr. Salgado-Pabón relocated the laboratory in 2019. Following graduation, Phuong will begin as a Postdoctoral Fellow in the lab of Dr. Heran Darwin at New York University.
In her free time, Phuong is a prolific reader. Her favorite books remain Anna Karenina and The Mists of Avalon. She enjoys hanging out at coffee shops and exploring new places with her husband, Ryan, and Luna's dog.