Gardnerella vaginalis small colony variants

阴道加德纳菌小菌落变种

基本信息

批准号：
10350711
负责人：
Joseph P Dillard
金额：
$ 19.44万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-02-15 至 2024-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10350711
关键词：
Adherence Affect Age Antibiotic Resistance Antibiotic Therapy Antibiotics Bacteria Bacterial Vaginosis Binding Cells Cervical Clinical DNA biosynthesis Disease Epithelial Epithelial Cells Exocervix Female Genital Diseases Female of child bearing age Frequencies Gardnerella Gardnerella vaginalis Growth Hospitals Hour Human In Vitro Infection Lactobacillus Lead Measurement Measures Metabolism Microbial Biofilms Modeling Mucous body substance Multiple Pregnancy Neisseria gonorrhoeae Neuraminidase Organ Culture Techniques Pathogenesis Patients Phase Pregnancy Complications Production Property Protein Biosynthesis Proteome Proteomics Recurrence Scanning Electron Microscopy Sexual Health Sexual Transmission Sexually Transmitted Diseases Stimulus Testing Tissues Toxic effect Toxin Universities Vagina Variant Virulence Virulence Factors Wisconsin Woman adverse pregnancy outcome dysbiosis mutant pathogen recurrent infection reproductive response trait

项目摘要

PROJECT SUMMARY Bacterial vaginosis (BV) is the most common gynecological disorder in women of childbearing age and is associated with adverse pregnancy outcomes and enhanced transmission of sexually-transmitted diseases. Gardnerella vaginalis is the signature bacterial species associated with BV, but its mechanisms of infection and persistence are not well understood. Furthermore, the mechanisms by which G. vaginalis infection recurs after antibiotic treatment are not known. We have discovered that G. vaginalis grows in two different forms, as a slow-growing small colony variant (SCV) and as a faster-growing large colony variant (LCV). The SCV form produces more of the toxin vaginolysin, is more antibiotic resistant, and is more inhibitory to the growth of Lactobacillus spp. The LCV produces more biofilms and is more inhibitory to the growth of Neisseria gonorrhoeae. Preliminary proteomic analyses indicate that SCVs downregulate DNA replication and protein synthesis and upregulate vaginolysin and other putative virulence factors. We hypothesize that the SCV is a form of the bacteria primed for initiating infection or for persisting under adverse conditions, while the LCV gives faster multiplication and builds the biofilm that supports multiple BV-associated pathogens. For these studies, we will characterize differences in infection abilities of the SCVs and make mutants to characterize the key factors involved in the increased virulence and altered metabolism of the variant form. Pathogenesis studies will include infection of human cervical tissue in organ culture. We will identify mechanisms involved in persistence and survival in adverse conditions using proteomics and measurements of antibiotic resistance, and we will identify factors stimulating phase variation.

项目摘要细菌性阴道病（BV）是育龄女性中最常见的妇科疾病，IS 与不良妊娠结局有关，并增强了性传播疾病的传播。阴道加德纳（Gardnerella daginalis）是与BV相关的签名细菌物种，但其感染机制持久性并不理解。此外，神阴道感染的机制抗生素治疗后尚不清楚。我们发现，阴道G. g。以两种不同的形式生长，生长缓慢的小菌落变体（SCV），作为一个更快的大菌群变体（LCV）。 SCV形式产生更多的毒素阴道素，具有抗生素耐药性，对生长更具抑制作用乳杆菌属。 LCV产生更多的生物膜，对奈瑟氏菌的生长更具抑制作用淋病。初步蛋白质组学分析表明，SCV下调DNA复制和蛋白质合成和上调阴道素和其他推定的毒力因子。我们假设SCV是启动感染或持续存在的细菌形式，而LCV 给出更快的乘法并构建支持多个BV相关病原体的生物膜。为此研究，我们将表征SCV的感染能力差异，并使突变体的特征毒力增加并改变了变体形式的代谢涉及的关键因素。发病研究将包括在器官培养中感染人宫颈组织。我们将确定涉及的机制使用蛋白质组学和抗生素耐药性测量在不利条件下的持久性和生存率，我们将确定刺激相变的因素。