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Estrogen signaling contributes to Group B Streptococcal disruption and invasion of brain endothelial cell

16.01.2024 12:30 Uhr 14:00 Uhr CMFI Invited Speaker Nadine Vollmuth

Sprecherin: Nadine Vollmuth, University of Alabama

Gastgeber: Andreas Peschel (CMFI)

Datum & Uhrzeit: 16.01.2024 | 12:30 – 2 pm

Ort:  Hörsaal N06, Hörsaalzentrum



Bacterial meningitis is a serious life-threatening infection of the central nervous system (CNS) that occurs when blood-borne bacterial pathogens can disrupt the blood-brain barrier (BBB) and enter the CNS. The BBB is comprised of highly specialized brain endothelial cells (BEC) that serve to protect the CNS from toxins and pathogens while supporting proper brain function. Group B Streptococcus (GBS) is the leading cause of neonatal meningitis and mechanisms of how the BBB fails to protect the CNS during infection remain unclear. We have conducted microRNAseq on BECs either infected with GBS or mock infected and strikingly we found that globally microRNAs are downregulated. Estrogen signaling has been demonstrated to contribute to global microRNA downregulation and we hypothesize that estrogen signaling may play a role in GBS – BEC disruption. Our preliminary findings demonstrate that treatment of BECs with estrogen receptor (ER) antagonists is sufficient to inhibit GBS invasion of BECs and rescue candidate microRNA expression. Additionally, we find that BECs treated with the ER agonist beta-estradiol is sufficient to reduce microRNA expression, reduce trans-endothelial electrical resistance, and increase rates of bacterial invasion. Our findings suggest that GBS may utilize estrogen signaling to gain access to the CNS and cause bacterial meningitis. These results are supported by population-based observations that mothers on perinatal hormone treatment have higher rates of neonates that experience invasive GBS disease. Future work will elucidate mechanisms of global microRNA failure and determine if rescue of microRNAs can restore BBB function during GBS infection. Additionally, we will determine if GBS produces an estrogen-like molecule to induce ER signaling or if GBS induces endogenous ER signaling. We show for the first time, that ER signaling can contribute to GBS invasive disease.