Genetic screen to define the regulation of beta-hemolysin toxin expression in Streptococcus agalactiae

基因筛选以确定无乳链球菌中 β-溶血素毒素表达的调节

基本信息

批准号：
10731405
负责人：
Natalia Korotkova
金额：
$ 19.13万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-05-19 至 2025-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10731405
关键词：
Abbreviations Adult Agar Antibiotic Prophylaxis Antibiotic Resistance Bacteria Binding Blood Blood - brain barrier anatomy Blood Circulation Cell Separation Central Nervous System Chemicals Colon Culture Media Cytolysins Detection Development Disease Endothelium Environment Epithelium Family Folic Acid Gene Expression Genes Genetic Screening Genetic Transcription Goals Gram-Positive Bacteria Hemolysin Human Immune Immune Evasion Immunocompromised Host Induction of Apoptosis Infection Invaded Libraries Lipids Meningitis Mothers Neonatal meningitis Newborn Infant Niacinamide Nutrient Oligopeptides Pathway interactions Peptide Sequence Determination Peptides Phagocytes Phagocytosis Induction Pigments Pregnant Women Preventive measure Production Proteins Regulation Repression Research Sepsis Sequence Determination Serum Signal Transduction Small Intestines Starch Streptococcal Infections Streptococcus Group B System Testing Therapeutic Toxin Vaccines Virulence Virulence Factors Water Work blood-brain barrier disruption clinically relevant gastrointestinal genomic locus gut microbiota in vivo inhibitor inorganic phosphate intestinal epithelium metabolomics microbiome microbiota microorganism mutant neonatal sepsis novel novel therapeutics older patient pathogen placental membrane prevent quorum sensing screening small molecule transcriptome sequencing transmission process treatment group vaginal microbiota

项目摘要

Group B Streptococcus (GBS) is a normal constituent of the intestinal and vaginal flora in 15–30% of healthy adults. The bacterium can, however, cause infections in elderly and immunocompromised patients, and pregnant women, and is the main cause of fatal invasive disease in newborns. GBS translocation through epithelial, endothelial, and placental barriers is facilitated by a pore-forming toxin β-hemolysin, also known as the β-hemolytic pigmented lipid or granadaene. To identify factors involved in the regulation of β-hemolysin expression we developed new peptide-free culture media for screening of a transposon mutant library of GBS CJB111. The pilot screens identified nine novel genetic loci associated with positive and negative modulation of β-hemolysin expression. Based on preliminary findings, we hypothesize that GBS possesses a regulatory mechanism that tailors β-hemolysin expression to the environment. To unravel the mechanism, we will employ transposon mutant library screening, RNA-seq and metabolomics analyses, isolation, and de novo sequence determination of secreted peptide-based repressors. The results of this exploratory work have the potential to lead to the development of a novel inhibitor of the invasion state of GBS.

B 族链球菌 (GBS) 是肠道和阴道菌群的正常组成部分然而，该细菌可导致 15-30% 的健康成年人感染。免疫功能低下的患者和孕妇，是致命的侵袭性病毒的主要原因新生儿 GBS 易位通过上皮、内皮和胎盘屏障。由成孔毒素 β-溶血素（也称为 β-溶血色素脂质）促进为了确定参与调节 β-溶血素表达的因素，我们开发新的无肽培养基用于筛选 GBS 转座子突变体库 CJB111。试点筛选确定了与阳性和阴性相关的九个新基因位点。根据初步发现，β-溶血素表达的负调节。 GBS 具有调节 β-溶血素表达的调节机制为了揭示这一机制，我们将采用转座子突变体库筛选， RNA-seq 和代谢组学分析、分离和从头序列测定这项探索性工作的结果有潜力导致 GBS 侵袭状态的新型抑制剂的开发。