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17β-Estradiol Mediates Staphylococcus aureus Adhesion in Vaginal Epithelial Cells via Estrogen Receptor α-Associated Signaling Pathway

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Abstract

Staphylococcus aureus, a major opportunistic pathogen in aerobic vaginitis (AV), can potentially invade the host and occasionally cause infections. Estrogen is associated with an altered immune response of vaginal epithelial cells and prevention of certain vaginal infectious diseases. However, the molecular mechanisms involving estrogen and S. aureus adhesion to vaginal epithelial cells remain unclear. Thus, here, VK2/E6E7 vaginal epithelial cells were infected with S. aureus, and the role of the estrogen receptor α-associated signaling pathway (ERα/FAK/Src/iNOS axis) in S. aureus adhesion was evaluated. The estrogen-associated phosphorylation status of ERα, FAK, and Src and the protein level of iNOS were assessed by western blotting. We used a specific ERα inhibitor to validate the involvement of the ERα-associated signaling pathway. The results showed that with exposure to 1 nM estrogen for 24 h, transient ERα-associated pathway activation was observed, and the protein expression upregulation was accompanied by a dose-dependent increase in 17-β-estradiol (E2) content and increased S. aureus adherence to vaginal epithelial cells. Estrogen-induced activation of the ERα/FAK/Src/iNOS axis was notably inhibited by the specific ERα inhibitor (ICI 182780). Simultaneously, a significant decrease in the number of adherent S. aureus was observed. However, this inhibitory effect diminished after inhibitor treatment for 24 h. Our findings suggested that the ERα-associated signaling pathway might be involved in S. aureus adherence to vaginal epithelial cells, which appeared to be linked to enhanced cell adhesion leading to AV.

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Acknowledgements

We thank the medicine research center of Women's Hospital of Nan**g Medical University for technical, and equipment supports. We are also grateful to Nan**g Medical University for financial supports and excellent technical assistance.

Funding

This research was financially supported by National Natural Science Foundation of China (82071602, 81671410), Jiangsu provincial key research and development program BE2021613, and science and technology fund of Nan**g medical university (NMUB2018070).

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  1. Lina Yan, Can Rui, and Bin Zhuang contribute to this paper equally.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Women’s Hospital of Nan**g Medical University, Nan**g Maternity and Child Health Care Hospital, Nan**g, 210004, People’s Republic of China

    Lina Yan, Can Rui, Ting Luan, Lisha Jiang, Zhiyong Dong, Qing Wang, Aiwen Wu, ** Li, **nyan Wang & **n Zeng

  2. Department of Pediatrics, Women’s Hospital of Nan**g Medical University, Nan**g Maternity and Child Health Care Hospital, Nan**g, 210004, People’s Republic of China

    Bin Zhuang

  3. Department of Obstetrics and Gynecology, Jiangsu Taizhou People’s Hospital, Taizhou, 225300, People’s Republic of China

    **a Liu

  4. Department of Obstetrics and Gynecology, Changzhou Maternity and Child Health Care Hospital Affiliated to Nan**g Medical University, Changzhou, 213003, People’s Republic of China

    Lina Yan

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  1. Lina Yan
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Contributions

PL, XW and XZ conceived and designed this study, and are corresponding authors. LY, XL, and TL carried out the experiments. LJ, ZD, QW and AW performed data collection and analysis. LY, CR, and BZ wrote and edited the manuscript, and they contributed equally to this study. All authors have read and approved the final manuscript and, therefore, have full access to all the data in the study and take responsibility for the integrity and security of the data.

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Correspondence to Lina Yan.

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Yan, L., Rui, C., Zhuang, B. et al. 17β-Estradiol Mediates Staphylococcus aureus Adhesion in Vaginal Epithelial Cells via Estrogen Receptor α-Associated Signaling Pathway. Curr Microbiol 80, 391 (2023). https://doi.org/10.1007/s00284-023-03488-6

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