Role of bacteriophage in Neisseria gonorrhoeae biology

描述(申请人提供)：淋球菌包含9个基因岛，编码噬菌体。这些噬菌体在淋球菌生物学中扮演的角色尚不清楚。生物信息学分析表明，这些岛在所有淋球菌株中高度保守，在大多数共生奈瑟氏菌中缺失。转录组分析表明，它们的表达发生了调节，许多噬菌体基因在模拟体内生长条件(低氧或低铁，或在胁迫下)生长的条件下上调。这项提议的目标是破译噬菌体编码的基因如何对淋球菌生物学做出贡献。由于一些噬菌体编码的蛋白与已知的破坏紧密连接的蛋白有显著的同源性，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入侵组织。为了验证这一假设，我们将构建各种缺失突变体，生成一组缺乏一个或多个淋球菌噬菌体基因组/基因的菌株，并测试这些突变体入侵极化上皮细胞和在极化上皮细胞之间交叉的能力。 公共卫生相关性：已知噬菌体可导致多种疾病。虽然人们很早就知道，大多数致病奈瑟菌菌株都含有大量的基因岛，这些基因岛似乎是来自温带和丝状噬菌体的溶原菌，但直到最近的生物信息学和转录组分析，才有足够的数据表明，这些噬菌体可能会影响奈瑟菌生物学中的毒力。该项目旨在确定这些噬菌体在淋球菌生物学中扮演的角色(如果有的话)。

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. PUBLIC HEALTH RELEVANCE: Bacteriophage have been known to contribute to a variety of diseases. While it has been known for a long time that most pathogenic Neisseria strains contain numerous genetic islands that appear to be lysogens from temperate and filamentous bacteriophages, it wasn't until recent bioinformatic and transcriptome analysis that there was enough data to suggest that these phage could impact on virulence in neisserial biology. This project is designed to determine what role, if any, these phage play in gonococcal biology.