The Pathogenesis Of Streptococcus anginosus In Aerobic Vaginitis

Abstract

Zhi Tao,1,2 Lei Zhang,2 Qiongqiong Zhang,1,2 Tao Lv,2 Rui Chen,1,2 Lijun Wang,2 Zhenyu Huang,1,2 Long Hu,1 Qinping Liao2 1School of Clinical Medicine, Tsinghua University, Beijing 100084, People’s Republic of China; 2Department of Obstetrics and Gynecology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, People’s Republic of ChinaCorrespondence: Qinping LiaoDepartment of Obstetrics and Gynecology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Litang Road No. 168, Changping District, Beijing 102218, People’s Republic of ChinaTel/Fax + 86 10 5611 8901Email qinping_liao@163.comBackground: Aerobic vaginitis (AV) is a newly defined type of bacterial vaginitis, but its pathogenesis is not yet clear. Streptococcus anginosus appears as an emerging pathogen in recent case reports, and colonizes in vagina of patients with AV. In this study, we investigate the pathogenesis of S. anginosus in AV.Materials and methods: (1) We collected 41 vaginal specimens from 21 healthy, fertile women with normal vaginal flora (NM), 10 with bacterial vaginosis (BV) and 10 with AV; their microbiome structure was analysed by 16S rRNA gene sequencing. (2) S. anginosus and vaginal epithelial cells were cocultured in vitro, and cytotoxicity was tested by an LDH kit. (3) The S. anginosus virulence gene sag was knocked out, and the cytotoxicity of the mutant in vaginal epithelial cells was tested.Results: (1) The microbiome structure of AV was dramatically different from that of BV and NM. The predominant genera of the three groups were Streptococcus spp., Gardnerella spp. and Lactobacillus spp. Streptococcus spp. were significantly more abundant in AV than in BV (95% CI [0.1391, 0.8676], P<0.01) and NM (95% CI [0.1391, 0.8676], P<0.01). (2) S. anginosus was the dominant species in AV (95% CI [0.04672, 0.1097], P<0.01). (3) The mean cytotoxicity of S. anginosus in vaginal epithelial cells was 58.34% for the wild type (WT) and 16.43% for the mutant; this difference was significant (95% CI [−60.55, −23.28], P<0.01).Conclusion: S. anginosus was the predominant microorganism in patients with AV in our study. S. anginosus caused vaginal epithelial cell lysis, indicating that S. anginosus is an AV pathogen. The S. anginosus virulence gene sag is vital for vaginal epithelial cell lysis.Keywords: Streptococcus anginosus, aerobic vaginitis, vaginal microbiome, gene knockout, next-generation sequencing technology, NGS