Meet the Scientist
Dr. Kelly Doran
Professor
Department of Immunology & Microbiology
Pregnancy, Newborns, and a Hidden Microbial Team-Up Behind Dangerous Infections
Bacterial pathogens can cause infections on their own, but did you know that they can partner up with other microbes in ways that amplify their disease-causing potential? Scientists often study disease-causing microbes individually, but in reality, pathogens encounter many other microorganisms while infecting the human body. Communities of microbes, collectively called the “microbiota”, naturally live in areas such as the mouth, skin, intestines, and vaginal tract in humans. A new and important area of study is how these members of the microbiota communicate with disease-causing microbes, potentially making them able to grow, persist, or cause infection.
Group B Streptococcus (GBS), also known as Streptococcus agalactiae, is a bacterium that lives in the gastrointestinal tracts and reproductive tracts of healthy people. Most of the time, GBS lives in people without causing illness, including in up to 20% of pregnant individuals. However, it can cause serious complications during pregnancy and severe infections in newborns. In fact, GBS is one of the leading causes of bacterial infections in newborns worldwide.
During pregnancy, GBS can travel from the vaginal tract up into the uterus, contributing to serious complications such as preterm birth and still birth. It can also be transmitted to newborns and cause life-threatening infections. But what flips the switch that transforms GBS from a relatively harmless resident to a migrating, disease-causing microbe? The Doran Lab is currently investigating this question in hopes of finding ways to prevent this migration from occurring in the first place.
Candida albicans is a species of fungus that also commonly lives in the human body as part of the normal microbiota. Many studies have found GBS and C. albicans living together in the vaginal tract at the same time, almost like roommates. The Doran lab wants to understand whether this partnership— GBS living closely with C. albicans— helps transform GBS from “friend” to “foe”. To find this out, Kelly and members of her lab, Shirli Cohen and Ari Crossen, joined forces with Dr. Kyla Ost, a Candida expert and assistant professor in the Department of Immunology and Microbiology.
How does the Doran Lab study interactions between GBS and C. albicans?
The Doran Lab has multiple tools in their toolkit to study interactions between GBS and C. albicans. Kelly and her team have developed a mouse model in which both species are present in the vaginal tract. They can also grow human vaginal cells in the laboratory and expose them to GBS and C. albicans, allowing the researchers to study interactions in an environment that resembles the vaginal tract. Lastly, her team can examine changes in the gene expression of these microbes when they’re teamed up in the presence of one another. This provides a “blueprint” of how the two microbes change behavior when they become vaginal tract roommates.
What have Kelly and her team discovered so far, and how can these findings translate into therapeutics?
Kelly and her team have found that C. albicans helps GBS grow and persist in the vaginal tract in several ways. C. albicans cells can grow in either a “yeast” form consisting of round or oval cells, or a “hyphal” form, consisting of long threadlike structures. Switching between these forms helps C. albicans adapt to different environments. The Doran Lab found that C. albicans hyphae structures provide a surface where GBS can gather, grow, and attach to human cells. Think of floating logs in water that provide birds a place to land and congregate. These interactions help GBS to establish itself in the vaginal tract and migrate up to the uterus, where it can cause infection. The Doran Lab also found that interactions with C. albicans helped shield GBS from antibiotics.
Kelly and her team also uncovered an interesting exchange occurring between C. albicans and GBS. Physical contact with GBS prompted C. albicans to increase its production of arginine, an amino acid that serves as a building block for proteins. Arginine can act as an alarm signal for GBS, causing it to activate genes that help it survive. These include genes that produce adhesins, which are molecules that help GBS attach more effectively to both C. albicans and human vaginal cells. This cooperation helps GBS to grow and persist in the vaginal tract while priming it to cause infection.
Where are the next steps for this research?
Current treatments typically target one microbe at a time, and the Doran Lab hopes to identify new therapeutics that disrupt harmful partnerships between microbes. Preventing these interactions could ultimately reduce the risk of GBS infections during pregnancy and in newborns.
Of course, there are many more unanswered questions to explore. Kelly and her lab want to know how other members of the vaginal microbiota affect interactions between GBS and C. albicans. They also want to investigate how this GBS-C. albicans partnership changes how the host immune systems responds to these microbes Answering these questions could uncover how complex microbial communities influence infection risk and help researchers develop new approaches to protect pregnant people and newborns from infection by GBS.
If you want to learn more about the scientist, please head to their official CU webpage
If you want to learn more about the research, please go to the lab website