Gardnerella vaginalis

Vaginolysin—An Iron-Regulated Toxin#

Vaginolysin (VLY) is a cholesterol-dependent cytolysin (CDC) that is G. vaginalis's primary virulence factor. VLY forms pores in human vaginal epithelial cells by binding to the cholesterol-rich membrane complement regulatory molecule CD59.

VLY expression is iron-regulated—iron availability modulates vaginolysin production, connecting Gardnerella virulence to the mucosal iron landscape controlled by Lactoferrin.^{[1]Roberts 2019 — Mucosal Lactoferrin Response to Genital Tract Infections Is Associated with Iron and Nutritional BiomarkersS. A. Roberts, L. Brabin, S. Diallo et al. · 2019Open reference 1 ↓}

Statin repurposing: Because VLY requires membrane cholesterol for binding, statins (which deplete membrane cholesterol) can reduce vaginolysin cytotoxicity. Simvastatin at sub-antimicrobial doses significantly reduces G. vaginalis biofilm virulence in vitro.^{[2]Abdelmaksoud 2017 — Association between Statin Use, the Vaginal Microbiome, and Gardnerella vaginalis Vaginolysin-Mediated CytotoxicityAbdelmaksoud AA, Girerd PH, Garcia EM et al. · 2017Open reference 2 ↓} This is a Cureva-relevant drug repurposing lead.

Disease Associations#

BV: The defining organism—clue cells (vaginal epithelial cells coated with G. vaginalis) are a diagnostic criterion.^{[3]Ughade 2024 — Navigating the Microbial Landscape: Understanding Dysbiosis in Human Genital Tracts and Its Impact on FertilityPrachi A. Ughade, Deepti Shrivastava, Kamlesh Chaudhari · 2024Open reference 3 ↓}

HPV persistence: G. vaginalis-dominant vaginal microbiomes associated with HPV16 persistence.^{[4]Yang 2020 — Vaginal Microbiome Alterations in HPV16 Infection by Shotgun MetagenomicsQian Yang, Yaping Wang, Xinyi Wei et al. · 2020Open reference 4 ↓} Preterm birth: BV and G. vaginalis abundance associated with preterm birth risk.^{[5]Pruski & Correia 2021 — Direct On-Swab Metabolic Profiling of Vaginal Microbiome Host Interactions During Pregnancy and Preterm BirthPamela Pruski, Gonçalo D. S. Correia, Holly V. Lewis et al. · 2021Open reference 5 ↓}

Male infertility: Detected in semen; associated with impaired sperm quality.^{[6]Magill 2023 — Male Infertility and the Human MicrobiomeMagill RG, MacDonald SM · 2023Open reference 6 ↓} Prostatitis: Part of the prostatitis-associated urogenital microbiome.^{[7]Magri 2018 — Multidisciplinary Approach to ProstatitisVittorio Magri, Matteo Boltri, Tommaso Cai et al. · 2018Open reference 7 ↓} PCOS: Part of PCOS-associated vaginal microbiome shifts.^{[8]Zheng 2024 — Differential enrichment of bacteria and phages in vaginal microbiomes in PCOS and obesity: shotgun sequencing analysisZheng S, Chen H, Yang H et al. · 2024Open reference 8 ↓}

Endometriosis: Depleted in cervical samples (see genus page Gardnerella).