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

Abstract

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.IMPORTANCESneathia vaginalis (S. vaginalis) is a bacterial species that lives in the human vagina and can cause complications during pregnancy if it invades the uterus. It is capable of killing cervical epithelial cells. Human papillomaviruses (HPV) are sexually transmitted viruses that can cause genital lesions and cervical cancer. Recently, multiple reports describe an association between S. vaginalis and HPV. This study used cultured cervical epithelial cells expressing the high-risk HPV type, HPV16, and HPV-negative cells to determine whether HPV promotes the growth of S. vaginalis. We found that HPV16 promotes the survival of cervical epithelial cells that are exposed to S. vaginalis. Survival of cervical epithelial cells may benefit the growth of S. vaginalis, which adhere to and feed off of these cells to survive in the female reproductive tract.