Urinary tract infections (UTI) are a costly clinical problem that affects millions of women worldwide. We are approaching this problem in a new way by focusing on vaginal bacteria.
Vaginal genera—most frequently Gardnerella or Lactobacillus—have been frequently isolated from urine collected directly from the bladder in women. Gardnerella is present at high levels in the vagina in women with bacterial vaginosis (BV), which itself is linked with UTI. Our mouse models show that Gardnerella acts as a “covert pathogen” in the urinary tract, triggering apoptosis and exfoliation of the bladder epithelium and worsening UTI. This could help explain why BV is associated with UTIs and suggests that vaginal bacteria might impact UTI outcomes in ways we have not fully understood before.
We are using in vivo and in vitro models to define the mechanisms of Gardnerella pathogenesis in the urinary tract. We are also analyzing clinical samples to specify the association between Gardnerella in the vagina and epithelial exfoliation and UTI in women. We hope our work will lead to new vaginally focused screening strategies to identifying women at risk of UTI and improve prevention and treatment.
Research shows that women with high levels of bacterial vaginosis (BV) are more likely to have persistent HPV infections, which can lead to cervical cancer. However, we still don’t fully understand how BV might cause cervical cancer. There is limited information on how BV bacteria and HPV interact because we lack suitable study models.
We are working with Jiafen Hu, MSc, PhD (Penn State) and Kristine Wylie, PhD (WashU) to create a model that simulates both BV and HPV infections to better understand their relationship in cervical cancer. We hypothesize that BV bacteria might help HPV infections and cancer progress, and that contraceptives might worsen HPV persistence and cancer by altering the vaginal microbiome.
Our ongoing research is looking at whether BV bacteria contribute to HPV persistence and cancer by damaging the vaginal mucus barrier, affecting the vaginal lining, or altering the immune response. We are also studying if hormonal contraceptives encourage HPV persistence and cancer by disrupting the vaginal microbiome. These studies aim to provide a foundation for deeper research into how BV and HPV are linked in cervical cancer.
The vaginal microbiome influences the risk of adverse perinatal outcomes (APO), including preterm birth, being small for gestational age and neonatal sepsis. While many studies focus on how infections and inflammation directly affect the fetus, our research investigates whether vaginal bacteria increase these risks without directly causing infections.
We use Gardnerella in our studies because it is common in the vagina, especially in women with bacterial vaginosis (BV) and is linked to adverse pregnancy outcomes. In experiments with pregnant mice, we found that introducing Gardnerella into the vagina led to infections by other pathogens and caused inflammation in the placenta, even though Gardnerella itself was not found in the upper reproductive tract at the time of these issues.
Our ongoing research aims to understand how Gardnerella and other BV-associated bacteria affect the placenta and the baby. We hope this will lead to better screening and treatment strategies to improve pregnancy outcomes.
Catheter-associated urinary tract infections (CAUTIs) are a major and costly problem affecting many patients. These infections involve both the bladder and the catheter, making them hard to treat. While antibiotics have been used to try to reduce bacterial growth on catheters, rising antibiotic resistance means we need new solutions.
Lactobacilli probiotics show promise because they can compete with harmful bacteria for adhesion and produce substances that kill pathogens. We have used 3D-bioprinting to create a prototype catheter that includes the probiotic Lactobacillus rhamnosus GG.
Our tests show that this prototype:
- Keeps the probiotic alive over time
- Continuously releases L. rhamnosus, lactic acid, and hydrogen peroxide
- Forms beneficial biofilms on the catheter surface
- Blocks uropathogenic E. coli in vitro
- Remains viable in a mouse model
We are continuing to refine this design and test its safety and effectiveness. If successful, this project will produce 3D-printed catheters that deliver probiotics for preventing and treating CAUTIs.
Intracellular infections from Gram-negative bacteria are a major global health concern. Our research shows that Nur77 helps protect the bladder from infections caused by uropathogenic Escherichia coli (UPEC), which is a leading cause of urinary tract infections (UTIs). Mice lacking Nur77 develop more UPEC bacterial clusters in their bladder cells, leading to chronic infections.
On the other hand, using a Nur77-boosting drug called cytosporone B prevents UPEC from entering bladder cells, helps clear the bacteria from urothelial cells in vitro and reduces UPEC intracellular infections in mice. This suggests that targeting Nur77 could be a new way to treat UTIs without relying on traditional antibiotics.
We are continuing to study how Nur77 affects bacterial trafficking and immune responses to UTIs.
With generous support …
Work in the Gilbert lab is supported by NIH R01s and an R03 from the NIDDK and an R21 from the NCI.
We are thankful for past support from an NIDDK K01 fellowship, the Center for Women’s Infectious Disease Research (cWIDR), the Children’s Discovery Institute, and the American Heart Association.