Associate Microbiologist, Department of Medicine
Brigham and Women's Hospital

robin.ross@channing.harvard.edu

My main research focus is the human vaginal microflora and its role in health and disease. My primary interests include the role of this microflora as a unit in maintaining a healthy vaginal environment and the virulence mechanisms of the following members of the microflora: Prevotella bivia, Staphylococcus aureus, and Group B Streptococcus (GBS). Currently, my research encompasses two separate projects: determining the role of the vaginal microflora in the development of bacterial vaginosis (BV) and elucidating the molecular mechanisms of growth-rate regulation in GBS.

BV is characterized by a disruption of the normal vaginal microflora that manifests in an abnormally high vaginal pH, a low concentration of Lactobacillus acidophilus, and a high concentration of Prevotella bivia, but the events that precede this state remain unclear. To determine the early stages of this disease, we developed an in vitro model of BV using vaginal and ectocervical epithelial cell lines and L. acidophilus and P. bivia. We are now using this model system to determine the interaction between vaginal bacteria and eukaryotic cells. These studies focus on attachment and internalization of each organism and the cytokine responses of the cell lines. In similar studies, we are using a mix of vaginal microflora to establish responses under normal conditions. Initial results from studies of mixed microflora have shown that even though the rate of adherence of P. bivia is lower than that of L. acidophilus, P. bivia is internalized at a higher rate, demonstrating a differential interaction of these organisms with the cell lines. In studies of pure cultures, L. acidophilus appears to suppress stimulation of both cell lines, as assessed by the production of NF-kB. Our goal for this work is to elucidate the mechanisms involved in the maintenance of a healthy host and to determine the changes that result in BV.

Another research focus is the regulation of virulence in GBS, a vaginal bacterium that is a leading cause of bacterial sepsis in neonates. We have determined that bacterial growth rate is the principal factor regulating expression of capsular polysaccharide (CPS), a virulence factor. The faster the organism grows, the more CPS there is its surface. These changes in expression of CPS occur rapidly after a change in growth rate. We also have shown that this regulation occurs at the level of gene transcription. Crude cell lysates from cultures stimulated to express CPS demonstrate the binding of a component to the promoter region of the CPS operon, thus suggesting the presence of a specific transcriptional regulatory molecule that controls the expression of these genes at rapid growth rates. We are continuing to purify and characterize this regulatory molecule, with the goal of defining the system regulating growth rate in GBS and possibly in other pathogenic organisms.

Ross RA, Lee ML, Delaney ML, Onderdonk AB. Mixed-effect models for predicting interactions in the vaginal ecosystem. J Clin Microbiol. 1994 Apr;32(4):871-5. [abstract]

Lee ML, Ross RA, Delaney ML, Onderdonk AB. Predicting abnormal microbial population levels in the vaginal ecosystem. Microb Ecol Hlth Dis 1994;7:235-240.

Lee ML, Ross RA, Onderdonk AB. Demonstration of microbial subgroups among normal vaginal microbiota data. Microb Ecol Hlth Dis 1995;8:107-112.

Ross RA, Lee ML, Onderdonk AB. Effect of Candida albicans infection and clotrimazole treatment on vaginal microflora in an in vitro. Obstet Gynecol. 1995 Dec;86(6):925-30. [abstract]

Ross RA, Lee ML, Delaney ML, Onderdonk AB. Use of continuous culture growth systems for modelling vaginal microflora behaviour. Microecology and Therapy, 1995;23:16-17.

Ross RA, Lee ML, Strategies for modeling microbial colonization of the human body in health and disease. In: Hurst, CJ, ed. Modeling Disease Transmission and Its Prevention by Disinfection. Cambridge, UK: Cambridge University Press, 1996, p.55-71.

Paoletti LC, Ross RA, Johnson KD. Cell growth rate regulates expression of group B Streptococcus type III capsular polysaccharide. Infect Immun. 1996 Apr;64(4):1220-6. [abstract]

Ross RA, Onderdonk AB. Activity of the antibiotic CP-99,219 (trovafloxacin) in a mixed microflora growth system model of intraabdominal infections in humans. Infect Dis Clin Pract 1996;5:S110-S112.

Lee ML, Ross RA, Onderdonk AB. Statistical models for vaginal microflora: identifying women at risk for group B Streptococcus colonization as a test concept. Infect Dis Obstet Gynecol 1997;5:336-340.

Paoletti LC, Pinel J, Johnson KD, Reinap B, Ross RA, Kasper DL. 1999. Synthesis and preclinical evaluation of glycoconjugate vaccines against group B Streptococcus types VI and VIII. J Infect Dis. 1999 Sep;180(3):892-5. [abstract]

Ross RA, Madoff LC, Paoletti LC. 1999. Regulation of cell component expression by growth rate in group B Streptococcus. J Bacteriol. 1999 Sep;181(17):5389-94. [abstract]

Ross RA, Onderdonk AB. 2000. Production of toxic shock syndrome toxin 1 by Staphylococcus aureus requires both oxygen and carbon dioxide. Infect Immun. 2000 Sep;68(9):5205-9. [abstract]