Virulence Factors of Stenotrophomonas maltophilia

嗜麦芽寡养单胞菌的毒力因子

• 批准号: 7739151
• 负责人: NICHOLAS P CIANCIOTTO
• 金额: $ 7.63万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-22 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7739151
• 关键词: Address; Bacteria; Behavior; Belief; Blood; Complement; Data; Disease; Enzymes; Eye; Fimbriae Proteins; Future; Genes; Genome; Grant; Heart; Human; Infection; Investigation; Lead; Legionella pneumophila; Locales; Lung; Modeling; Mus; Mutate; Nosocomial pneumonia; Organism; Pathogenesis; Pathology; Pilot Projects; Pilum; Pneumonia; Prevention; Protein Secretion; Proteins; Pseudomonas aeruginosa; Publishing; Research; Respiratory System; Respiratory Tract Infections; Respiratory tract structure; Role; Skin; Stenotrophomonas maltophilia; Surface; System; Testing; Tissues; Toxin; Type II Secretion System Pathway; United States National Institutes of Health; Urinary tract; Virulence; Virulence Factors; Virulent; Work; appendage; communicable disease diagnosis; disease diagnosis; genome sequencing; human disease; mutant; pathogen; programs; public health relevance; soft tissue

DESCRIPTION (provided by applicant): Stenotrophomonas maltophilia is an environmental bacterium that is implicated in an increasing spectrum of human disease, including infections of the lung, blood, heart, urinary tract, CNS, eyes, skin, and soft tissue. The respiratory tract is the most common locale for S. maltophilia, with ca. 5% of nosocomial pneumonias being associated with the organism. However, very little is known about the way in which S. maltophilia infects the lung. Thus, this proposal aims to identify S. maltophilia factors that promote lung infection and pathogenesis. Work from our lab and others have determined that type II protein secretion (T2S) is a major facilitator of virulence in lung pathogens, including Pseudomonas aeruginosa and Legionella pneumophila. Proteins secreted by T2S usually include toxins and tissue-degrading enzymes. Thus, we hypothesize that T2S is critical in S. maltophilia pathogenesis. To test this, we will mutagenize genes encoding the T2S apparatus that have been revealed by the sequencing of the S. maltophilia genome and then examine the mutants in the murine model of S. maltophilia lung infection. A reduction in the capacity of the mutants to infect and/or damage the lung would trigger the future pursuit of effectors. Other past work has shown that type IV pili (T4P) promote lung infection, and recent sequencing has also shown that S. maltophilia encodes this type of surface appendage. Thus, we posit that the T4P of S. maltophilia is another facilitator of disease. To address this, we will test T4P mutants of S. maltophilia for their behavior in the murine lung. The data obtained have the potential to lead to new forms of infectious disease diagnosis, treatment, or prevention. PUBLIC HEALTH RELEVANCE: Stenotrophomonas maltophilia is an environmental bacterium that has been implicated in an increasing spectrum of human infections, including infections of the lung, blood, heart, urinary tract, CNS, eyes, skin, and soft tissue. The respiratory tract is the most common locale for S. maltophilia, with approximately 5% of nosocomial pneumonias being associated with the organism. However, very little is known about the way in which S. maltophilia infects the lung. Thus, it is the intent of this proposed research to identify S. maltophilia factors that promote lung infection with a focus on the organism's type IV pili and the proteins secreted via the type II secretion system.

描述（由申请人提供）：嗜麦芽窄食单胞菌是一种环境细菌，与越来越多的人类疾病谱有关，包括肺、血液、心脏、尿路、CNS、眼睛、皮肤和软组织感染。呼吸道是链球菌最常见的部位。嗜麦芽窄食症，伴Ca. 5%的院内肺炎与该微生物有关。然而，很少有人知道的方式，S。嗜麦芽窄食菌会感染肺部因此，本建议旨在识别S。嗜麦芽因素促进肺部感染和发病。我们实验室和其他人的工作已经确定，II型蛋白分泌（T2 S）是肺病原体（包括铜绿假单胞菌和嗜肺军团菌）毒力的主要促进因素。由T2 S分泌的蛋白质通常包括毒素和组织降解酶。因此，我们假设T2 S在S.嗜麦芽窄食症发病机制为了验证这一点，我们将诱变编码T2 S装置的基因，这些基因已通过S. maltophilia基因组，然后在S.嗜麦芽窄食单胞菌肺部感染突变体感染和/或损害肺部的能力下降将引发未来对效应物的追求。其他过去的研究表明IV型皮利（T4 P）促进肺部感染，最近的测序也表明S.嗜麦芽窄食单胞菌编码这种类型的表面附属物。因此，我们认为S.嗜麦芽窄食症是另一种致病因素。为了解决这个问题，我们将测试S.嗜麦芽窄食单胞菌在鼠肺中的行为。获得的数据有可能导致新形式的传染病诊断，治疗或预防。公共卫生关系：嗜麦芽窄食单胞菌是一种环境细菌，与越来越多的人类感染有关，包括肺部、血液、心脏、尿路、中枢神经系统、眼睛、皮肤和软组织的感染。呼吸道是沙门氏菌最常见的场所。嗜麦芽窄食单胞菌，约5%的医院内肺炎与微生物有关。然而，很少有人知道的方式，S。嗜麦芽窄食菌会感染肺部因此，这是本研究的目的，以确定S。促进肺部感染的嗜麦芽窄食单胞菌因子，重点是生物体的IV型皮利和通过II型分泌系统分泌的蛋白质。