Quorum Sensing in H. influenzae otitis

流感嗜血杆菌中耳炎的群体感应

• 批准号: 6576267
• 负责人: Arnold Lee Smith
• 金额: $ 40.28万
• 依托单位: SEATTLE BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-20 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6576267
• 关键词: Haemophilus influenzae; bacteria infection mechanism; bacterial cytopathogenic effect; bacterial genetics; beta lactam antibiotic; beta lactamase; chinchilla; chloramphenicol acetyltransferase; enzyme linked immunosorbent assay; gene expression; host organism interaction; laboratory rat; macrolide antibiotics; mucins; mutant; otitis media; phase contrast microscopy; plasmids; protein biosynthesis; quinoline; serum; tetracyclines; tissue /cell culture; transcription factor; transfection; virulence; Haemophilus influenzae; bacteria infection mechanism; bacterial cytopathogenic effect; bacterial genetics; beta lactam antibiotic; beta lactamase; chinchilla; chloramphenicol acetyltransferase; enzyme linked immunosorbent assay; gene expression; host organism interaction; laboratory rat; macrolide antibiotics; mucins; mutant; otitis media; phase contrast microscopy; plasmids; protein biosynthesis; quinoline; serum; tetracyclines; tissue /cell culture; transcription factor; transfection; virulence

DESCRIPTION (provided by applicant): Otitis media with effusion (OME) is a significant health problem of children. Haemophilus influenzae is one of the major causes of this disease. Features of H. influenzae OME include frequent recurrences and a failure of eradication with antibiotic administration. One hypothesis explaining these features of H. influenzae OME is that the organism is growing as a biofilm in the middle ear. Bacterial biofilms are characteristically insensitive to antibiotic treatment, as well as incapable of elimination by the host inflammatory response. Evidence of a H. influenzae biofilm in children with OME consists of the presence of short-lived, Haemophilus-specific mRNA in the middle ear fluid of these children. Gram-negative bacterial biofilm formation is dependent upon the synthesis of quorum-sensing transcriptional activators, called autoinducers. We have found that H. influenzae; including those isolated from the middle ear possess a gene (HI0491) capable of synthesizing an autoinducer (AI-2). Insertional inactivation of HI0491 in the H. influenzae laboratory strain Rd KW20 results in a mutant, which lacks the ability to form mature biofilm structures, and has decreased susceptibility to antibiotics, a decreased conjugation frequency and decreased survival in an animal model of OME. In this application, we are seeking to characterize biofilm formation by several prototypic "otitic" H. influenzae in vitro, assess experimental OME caused by these strains in the weanling rat and chinchillas, determine the role of the autoinducer in this disease and define the role of AI-2 in biofilm development in vitro and in vivo. Understanding the role of AI-2 and biofilm formation in OME will permit strategies to prevent or treat this disease to be devised.

描述（由申请人提供）：带积液（OME）的耳炎是儿童的重大健康问题。流感嗜血杆菌是这种疾病的主要原因之一。流感烟草的特征包括频繁复发和抗生素给药的消除失败。一种解释了流感h。细菌生物膜特征对抗生素治疗不敏感，并且无法通过宿主炎症反应消除。 OME儿童中流感生物膜的h.;革兰氏阴性细菌生物膜的形成取决于被称为自动诱导剂的群体感应转录激活剂的合成。我们发现流感H.;包括从中耳分离的那些具有能够合成自动诱导剂（AI-2）的基因（HI0491）。 HI0491在流感流感实验室应变RD KW20中插入HI0491导致突变体，该突变体缺乏形成成熟的生物膜结构的能力，并且在OOME动物模型中降低了对抗生素的敏感性，结合频率降低和降低。 在此应用中，我们试图通过几种原型的“ Otitic” h。h。h。h。h。h。h. h. h. h. h. h. h. h. h. h。h. h。h。h. h。h. h。h。h。h。h。h。h。h。h. h. h. h。in in Betro in Betro in Betro，否则评估这些菌株在断奶大鼠和龙猫中引起的实验OME，确定自动诱导剂在该疾病中的作用，并确定AI-2在I-2中的作用在I-I-2在Vivo In Vivo中的作用。了解AI-2和生物膜形成在OME中的作用将允许设计或治疗该疾病的策略。