Doran Lab

Research

Vaginal Colonization

GBS vaginal colonization is a dynamic process; GBS must mediate complex interactions with host epithelium, and persist in the presence of normal microflora, host mucosal defenses and the female menstrual cycle.

Overall general key questions include:

  • What are the bacterial and host factors that lead to GBS vaginal persistence?
  • What is the role of host mucosal defenses in limiting GBS carriage?
  • Can novel therapeutics, such as probiotics or immunobiotics be used to reduce or limit GBS carriage, thus preventing transmission to the newborn?

We have developed a mouse model of GBS vaginal colonization. We typically observe nearly 100% colonization of mice within the first 24 hours post-inoculation and GBS persist for several weeks or up too several months depending on the stage of estrus, estradiol treatment regime, or specific mouse strain or bacterial strain used. In this model, we have visualization of GFP-GBS in the vaginal epithelium and lumen.

mouse model of GBS vaginal colonization

It is likely that bacterial Two Component Regulatory Systems (TCRS) play a particularly important role in GBS niche establishment and adaptation to various environments within the human host. Analysis of sequenced GBS genomes has revealed the presence of genes predicted to encode as many as 20 TCRS. A membrane-bound sensor histidine kinase senses environmental changes and subsequently activates its cognate cytoplasmic response regulator, which acts to modulate transcription. We have identified and investigated several key TCRS in GBS that promotes vaginal persistence. Continued studies seek to identify key regulated genes and the mechanisms that govern these interactions.

Two Component Regulatory Systems

Additionally we have characterized host immunity during vaginal colonization and have identified IL-17 production in response to long-term persistence. We continue to study the importance of this and other host responses to eventual GBS clearance.

 

 

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Doran Laboratory, University of Colorado.

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Lab Info
Research Complex 1 North
12800 E. 19th Ave., Rm. P18-9105

Kelly Doran, PhD
Professor of Immunology and Microbiology

(303) 724-3539
kelly.doran@ucdenver.edu