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Role of bacteriophage in Neisseria gonorrhoeae biology

噬菌体在淋病奈瑟菌生物学中的作用

基本信息

批准号：
8418698
负责人：
DANIEL C STEIN
金额：
$ 22.5万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-02-05 至 2015-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8418698
关键词：
Affect B-Lymphocytes Bacteriophages Bioinformatics Biological Assay Biological Models Biology Blood Clinical Collaborations Collection Complex DNA Sequence Data Disease Ectopic Pregnancy Epithelial Cells Epithelium Focal Infection Gene Expression Gene Expression Profile Genes Genetic Genome Genomic Islands Goals Gonorrhea Growth HIV Health Care Costs Hereditary Disease Homologous Gene Human In Vitro Infection Infection Control Infertility Inovirus Invaded Iron Island Lead Masks Methodology Mutagenesis Neisseria Neisseria gonorrhoeae Organism Outcome Oxygen Pathogenesis Pathogenicity Pelvic Inflammatory Disease Play Positioning Attribute Proteins Recording of previous events Regulation Research Research Personnel Role Route Series Stress Symptoms Testing Thinking Tight Junctions Time Tissues Toxin United States Vibrio cholerae Virulence Woman Work antimicrobial base chronic pelvic pain cost design in vivo innovation mutant polarized cell prevent programs therapy development tool transmission process vaccine development

项目摘要

DESCRIPTION (provided by applicant): Neisseria gonorrhoeae contains 9 genetic islands that encode for bacteriophage. The role that these bacteriophage play in gonococcal biology is unknown. Bioinformatic analysis indicates that these islands are highly conserved in all gonococcal strains and absent in most commensal Neisseria. Transcriptome analysis indicates that regulation of their expression occurs, and that many bacteriophage genes are upregulated when grown under conditions that would mimic in vivo growth conditions (Low oxygen or iron, or under stress). The goal of this proposal is to decipher how bacteriophage encoded genes contribute to gonococcal biology. Since some of the phage encoded proteins have significant homology with proteins that are known to disrupt tight junctions, we have hypothesized that these genes enhance the invasive capacity of gonococci. The hypothesis that we will be testing is that the expression of specific bacteriophage encoded-genes allow the gonococcus to invade into tissues by a paracellular route of invasion. To test this hypothesis, we will construct variou deletion mutants, generating a panel of strains that are deficient in one or more gonococcal phage genomes/genes and test these mutants for their ability to invade into and cross between polarized epithelial cells.

描述（由申请人提供）：淋病奈瑟菌包含9个编码噬菌体的基因岛。这些噬菌体在淋球菌生物学中的作用尚不清楚。生物信息学分析表明，这些岛屿在所有淋球菌菌株中高度保守，而在大多数共生奈瑟菌中不存在。转录组分析表明，当噬菌体在模拟体内生长条件（低氧或低铁或应激）的条件下生长时，它们的表达发生调控，许多噬菌体基因被上调。本提案的目标是破译噬菌体编码基因如何促进淋球菌生物学。由于一些噬菌体编码的蛋白质与已知破坏紧密连接的蛋白质具有显著的同源性，我们假设这些基因增强了淋球菌的侵袭能力。我们将要测试的假设是，特定噬菌体编码基因的表达允许淋球菌通过细胞旁入侵途径侵入组织。为了验证这一假设，我们将构建各种缺失突变体，产生一组缺乏一个或多个淋球菌噬菌体基因组/基因的菌株，并测试这些突变体侵入极化上皮细胞和在极化上皮细胞之间交叉的能力。