Sneathia: an emerging pathogen in female reproductive disease and adverse perinatal outcomes

Abstract

Sneathia is an emerging pathogen implicated in adverse reproductive and perinatal outcomes. Although scarce, recent data suggest that vaginally residing Sneathia becomes pathogenic following its ascension into the upper urogenital tract, amniotic fluid, placenta, and foetal membranes. The role of Sneathia in women's health and disease is generally underappreciated because the cultivation of these bacteria is limited by their complex nutritional requirements, slow growth patterns, and anaerobic nature. For this reason, molecular methods are typically required for the detection and differential diagnosis of Sneathia infections. Here, we review the laboratory methods used for the diagnosis of Sneathia infections, the molecular mechanisms underlying its virulence, and its sensitivity to antibiotics. We further review the evidence of Sneathia's contributions to the pathogenesis of bacterial vaginosis, chorioamnionitis, preterm prelabour rupture of membranes, spontaneous preterm labour, stillbirth, maternal and neonatal sepsis, HIV infection, and cervical cancer. Collectively, growing evidence indicates that Sneathia represents an important yet underappreciated pathogen affecting the development and progression of several adverse clinical conditions diagnosed in pregnant women and their neonates, as well as in non-pregnant women.

Keywords: Preterm birth; bacterial vaginosis; cervical cancer; preterm prelabour rupture of membranes (PPROM); vaginal biofilm.

Figure 1.. Sneathia in female reproductive disease

During pregnancy, Sneathia spp. are involved in the pathogenesis of preterm prelabor rupture of membranes, spontaneous preterm labor, clinical and histological chorioamnionitis, postpartum fever, as well as neonatal sepsis and bacteremia. In non-pregnant women, the presence of Sneathia spp. in the vaginal fluid is associated with bacterial vaginosis, HPV infection, cervical dysplasia, and increased risk of HIV infection and sexually transmitted diseases (STD).

Figure 2.. Potential Sneathia virulence factors

1. Pore-forming cytotoxin CptA (cytopathogenic toxin component A) could damage and/or lyse erythrocytes, vaginal and cervical epithelial cells, and cells of fetal membranes. Preliminary evidence is from in vitro studies of S. amnii [28, 65]. 2. Sneathia antigens may be sensed by vaginal and cervical antigen presenting cells and/or other immune cells causing inflammatory responses. Preliminary evidence is from microbial and immune mediator profiling of the human genital tract, transcriptional profiling of cervical antigen presenting cells, and in vitro co-culture studies of human vaginal epithelial cells and S. amnii or S. sanguinegens [72, 73]. 3. O-sialoglycoprotein endopeptidase may help Sneathia to transverse the cervix via cervical mucus. Preliminary evidence is from a genomic analysis of S. amnii [28].

Figure 3.. Putative mechanism of Sneathia ascending infection during pregnancy

Increased abundance of Sneathia in the vaginal microbiome facilitates biofilm formation and/or further spread of Sneathia to the cervical canal. Sneathia’s virulence factors affect the cervical epithelium and help the bacteria spread via cervical mucus. The putative invasins and pore-forming cytotoxin promote penetration of the chorioamniotic membranes and lead to intra-amniotic invasion. Further spread of Sneathia in the amniotic cavity and injury of amniotic cells promotes inflammation, leading to intra-amniotic infection.