Melissa Herbst-Kralovetz
Associate Professor, BIO5 Institute
Associate Professor, Basic Medical Sciences
Associate Professor, Clinical Translational Sciences
Associate Professor, Obstetrics and Gynecology
Primary Department
Department Affiliations
(602) 827-2247
Research Interest
Melissa Herbst-Kralovetz, PhD is an Associate Professor in the Departments of Basic Medical Sciences and Obstetrics and Gynecology and is Director of the Women's Health Microbiome Initiative at the UA College of Medicine-Phoenix. The Herbst-Kralovetz research lab is broadly interested in understanding innate mucosal immune responses to resident bacteria, pathogens (e.g HSV-2), and microbial products at mucosal sites, including the female reproductive tract. The mucosa provides a major immune barrier (physical, biological, and chemical) to microbial insult and her lab is interested in studying the mucosal barrier function of the lower female reproductive tract and its role in host defense against infection and inflammation as well as maintaining mucosal homeostasis. Dr. Herbst-Kralovetz has a long-standing interest and background in studying infections/conditions that impact women’s health.

Publications

Herbst, M. M., & Pyles, R. B. (2003). Immunostimulatory CpG treatment for genital HSV-2 infections. The Journal of antimicrobial chemotherapy, 52(6).
Yarbrough, V., Winkle, S., & Herbst-Kralovetz, M. (2013). Antimicrobial Peptides in the Female Reproductive Tract: A critical component of the mucosal immune barrier with physiological and clinical implications. Human Reproduction Update.
Muhleisen, A. L., & Herbst-Kralovetz, M. M. (2016). Menopause and the vaginal microbiome. Maturitas, 91, 42-50.

For over a century it has been well documented that bacteria in the vagina maintain vaginal homeostasis, and that an imbalance or dysbiosis may be associated with poor reproductive and gynecologic health outcomes. Vaginal microbiota are of particular significance to postmenopausal women and may have a profound effect on vulvovaginal atrophy, vaginal dryness, sexual health and overall quality of life. As molecular-based techniques have evolved, our understanding of the diversity and complexity of this bacterial community has expanded. The objective of this review is to compare the changes that have been identified in the vaginal microbiota of menopausal women, outline alterations in the microbiome associated with specific menopausal symptoms, and define how hormone replacement therapy impacts the vaginal microbiome and menopausal symptoms; it concludes by considering the potential of probiotics to reinstate vaginal homeostasis following menopause. This review details the studies that support the role of Lactobacillus species in maintaining vaginal homeostasis and how the vaginal microbiome structure in postmenopausal women changes with decreasing levels of circulating estrogen. In addition, the associated transformations in the microanatomical features of the vaginal epithelium that can lead to vaginal symptoms associated with menopause are described. Furthermore, hormone replacement therapy directly influences the dominance of Lactobacillus in the microbiota and can resolve vaginal symptoms. Oral and vaginal probiotics hold great promise and initial studies complement the findings of previous research efforts concerning menopause and the vaginal microbiome; however, additional trials are required to determine the efficacy of bacterial therapeutics to modulate or restore vaginal homeostasis.

Łaniewski, P., Gomez, A., Hire, G., So, M., & Herbst-Kralovetz, M. M. (2017). Human three-dimensional endometrial epithelial cell model to study host interactions with vaginal bacteria and Neisseria gonorrhoeae. Infection and immunity.

Colonization of the endometrium by pathogenic bacteria, ascending from the lower female reproductive tract (FRT), is associated with many gynecologic and obstetric health complications. To study these host-microbe interactions in vitro, we developed a human three-dimensional (3-D) endometrial epithelial cell (EEC) model using the HEC-1A cell line and rotating wall vessel (RWV) bioreactor technology. Our model, composed of 3-D EEC aggregates, recapitulates several functional/structural characteristics of human endometrial epithelial tissue including cell differentiation, junctional complexes/desmosomes, microvilli, membrane-associated mucins and Toll-like receptors (TLRs). TLR function was evaluated by exposing the EEC aggregates to viral and bacterial products. Treatment with polyinosinic-polycytidylic acid (poly(I:C)) and flagellin, but not with synthetic lipoprotein (FSL-1) or lipopolysaccharide (LPS), significantly induced proinflammatory mediators in a dose dependent manner. To simulate ascending infection, we infected EEC aggregates with commensal and pathogenic bacteria: Lactobacillus crispatus, Gardnerella vaginalis and Neisseria gonorrhoeae All vaginal microbiota and N. gonorrhoeae efficiently colonized the 3-D surface localizing to crevices of the EEC model and interacting with multiple adjacent cells simultaneously. However, only infection with pathogenic N. gonorrhoeae significantly induced proinflammatory mediators and significant ultrastructural changes to the host cells relative to other bacteria tested. This latter observation is consistent with clinical findings and illustrated the functional specificity of our system. Additionally, we highlighted the utility of 3-D EEC model to study N. gonorrhoeae pathogenesis using a well-characterized ΔpilT mutant. Overall, this study demonstrates that the human 3-D EEC model is a robust tool for studying host-microbe interactions and bacterial pathogenesis in the upper FRT.

Radtke, A. L., & Herbst-Kralovetz, M. -. (2012). Culturing and applications of rotating wall vessel bioreactor derived 3D epithelial cell models. J Vis Exp.