Human papillomavirus 16 mitigates Sneathia vaginalis-induced damage to cervical keratinocytes

Sneathia vaginalis is a bacterial component of the vaginal microbiome that is of clinical interest because of its association with preterm birth and other obstetric complications. It produces a cytotoxin, but little is known about the mechanism through which it kills epithelial cells or the role that cytotoxicity plays in bacterial survival. Recent microbiome studies demonstrate an association between S. vaginalis and human papillomavirus (HPV) within the female reproductive tract, suggesting that HPV and S. vaginalis could interact in some way within this shared niche. We analyzed 16S rRNA survey and HPV typing data from our Vaginal Human Microbiome Project and found, in agreement with other reports, that S. vaginalis was associated with HPV infection. To test the hypothesis that HPV promotes the growth of S. vaginalis, growth and cytotoxicity of S. vaginalis in co-culture with HPV16-positive and HPV-negative human cervical keratinocytes (HCK) were quantitatively assessed. Organotypic HCK rafts expressing HPV16 were more resistant to S. vaginalis-induced damage, as assessed by histology, and supported increased bacterial growth relative to HPV-negative HCK rafts. When S. vaginalis was co-cultured with HPV16-positive and HPV-negative HCK monolayers, cytotoxicity was observed in both HPV16-positive and HPV-negative cells, but HPV16-positive cells were more resistant to the toxic effects of the bacteria and supported bacterial growth for an extended period of time. In conclusion, HPV16 may protect cervical keratinocytes from the cytotoxic effects of S. vaginalis, preventing the eradication of colonized cells and supporting bacterial growth, and this could underlie the association between S. vaginalis and HPV in vivo.