Laboratory of Immunology and Cell Biology, Institute of Biotechnology, Life Sciences Center, Vilnius University, Vilnius, Lithuania.
Front Cell Infect Microbiol. 2020 Jan 10;9:452. doi: 10.3389/fcimb.2019.00452. eCollection 2019.
Bacterial vaginosis (BV) is a vaginal anaerobic dysbiosis that affects women of reproductive age worldwide. BV is microbiologically characterized by the depletion of vaginal lactobacilli and the overgrowth of anaerobic bacterial species. Accumulated evidence suggests that spp. have a pivotal role among BV-associated bacteria in the initiation and development of BV. However, spp. often colonize healthy women. is considered as a prevalent constituent of healthy vaginal microbiota, and is abundant in BV. spp. and secrete the toxins vaginolysin (VLY) and inerolysin (INY), which have structural and activity features attributed to cholesterol-dependent cytolysins (CDCs). CDCs are produced by many pathogenic bacteria as virulence factors that participate in various stages of disease progression by forming lytic and non-lytic pores in cell membranes or via pore-independent pathways. VLY is expressed in the majority of spp. isolates; less is known about the prevalence of the gene that encodes INY. INY is a classical CDC; membrane cholesterol acts a receptor for INY. VLY uses human CD59 as its receptor, although cholesterol remains indispensable for VLY pore-forming activity. INY-induced damage of artificial membranes is directly dependent on cholesterol concentration in the bilayer, whereas VLY-induced damage occurs with high levels of membrane cholesterol (>40 mol%). VLY primarily forms membrane-embedded complete rings in the synthetic bilayer, whereas INY forms arciform structures with smaller pore sizes. VLY activity is high at elevated pH, which is characteristic of BV, whereas INY activity is high at more acidic pH, which is specific for a healthy vagina. Increased VLY levels in vaginal mucosa were associated with clinical indicators of BV. However, experimental evidence is lacking for the specific roles of VLY and INY in BV. The interplay between vaginal bacterial species affects the expression of the gene encoding VLY, thereby modulating the virulence of spp. This review discusses the current evidence for VLY and INY cytolysins, including their structures and activities, factors affecting their expression, and their potential impacts on the progression of anaerobic dysbiosis.
细菌性阴道病（BV）是一种影响全球育龄妇女的阴道厌氧失调。BV 的微生物学特征是阴道乳杆菌的减少和厌氧细菌物种的过度生长。大量证据表明， spp. 在与 BV 相关的细菌中在 BV 的起始和发展中起关键作用。然而， spp. 通常定植于健康女性。 被认为是健康阴道微生物群的常见组成部分，并且在 BV 中丰富。 spp. 和 分泌毒素阴道溶血素（VLY）和内溶素（INY），它们具有归因于胆固醇依赖性细胞溶素（CDCs）的结构和活性特征。CDC 是许多致病菌产生的毒力因子，通过在细胞膜中形成溶细胞和非溶细胞孔或通过非孔依赖性途径参与疾病进展的各个阶段。VLY 在大多数 spp. 分离株中表达；关于编码 INY 的基因的流行率知之甚少。INY 是一种经典的 CDC；细胞膜胆固醇是 INY 的受体。VLY 使用人 CD59 作为其受体，尽管胆固醇仍然是 VLY 形成孔活性所必需的。INY 诱导的人工膜损伤直接依赖于双层中的胆固醇浓度，而 VLY 诱导的损伤发生在高胆固醇水平（>40mol%）下。VLY 主要在合成双层中形成膜嵌入的完整环，而 INY 形成具有较小孔径的弧形结构。VLY 活性在 BV 特征的较高 pH 下较高，而 INY 活性在更酸性 pH 下较高，这是健康阴道的特异性。阴道黏膜中 VLY 水平升高与 BV 的临床指标相关。然而，缺乏 VLY 和 INY 细胞溶素在 BV 中的特定作用的实验证据。阴道细菌物种之间的相互作用会影响编码 VLY 的基因的表达，从而调节 spp. 的毒力。本文综述了 VLY 和 INY 细胞溶素的现有证据，包括它们的结构和活性、影响其表达的因素以及它们对厌氧失调进展的潜在影响。
