Zevin Alexander S, Xie Irene Y, Birse Kenzie, Arnold Kelly, Romas Laura, Westmacott Garrett, Novak Richard M, McCorrister Stuart, McKinnon Lyle R, Cohen Craig R, Mackelprang Romel, Lingappa Jairam, Lauffenburger Doug A, Klatt Nichole R, Burgener Adam D
Department of Pharmaceutics, Washington National Primate Research Center, University of Washington, Seattle, Washington, United States of America.
National HIV and Retrovirology Labs, JC Wilt Center for Infectious Diseases, Public Health Agency of Canada, Winnipeg, Canada.
PLoS Pathog. 2016 Sep 22;12(9):e1005889. doi: 10.1371/journal.ppat.1005889. eCollection 2016 Sep.
The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity.
细菌群落影响对诸如艾滋病毒等传染病的易感性以及维持女性生殖道（FGT）健康的机制，目前还知之甚少。对FGT细菌的评估主要局限于物种丰度的研究，而非细菌功能。因此，我们试图使用宏蛋白质组学、宏基因组学和体外方法，在细菌性阴道病（BV）的背景下，研究细菌群落组成和功能与粘膜上皮屏障健康之间的关系。我们发现，以阴道加德纳菌为主导的高度多样化细菌群落与宿主上皮屏障破坏和免疫激活增强有关，而以乳酸杆菌属为主导的低多样性群落则与较低的 Nugent 评分、较低的pH值以及对维持上皮完整性很重要的宿主粘膜蛋白表达有关。重要的是，在没有临床BV诊断的情况下，与以阴道加德纳菌为主导的群落相关的上皮完整性破坏的蛋白质组学特征依然存在。由于传统临床评估未能捕捉到这一点，这可能代表了在阴道加德纳菌高流行人群中一种更大的未被充分认识的现象。我们最终证明，来自阴道加德纳菌的可溶性产物会抑制伤口愈合，而来自惰性乳酸杆菌的产物则不会，这为FGT细菌群落影响上皮屏障完整性的功能机制提供了见解。
