Virulence Factors of Stenotrophomonas maltophilia

描述(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有关，包括肺、血液、心脏、尿路、中枢神经系统、眼睛、皮肤和软组织的感染。呼吸道是嗜麦芽窄食单胞菌最常见的部位，约5%的医院获得性肺炎与细菌有关。然而，人们对嗜麦芽窄食单胞菌感染肺部的方式知之甚少。因此，本提案旨在确定促进肺部感染和致病的嗜麦芽窄食单胞菌因子。我们实验室和其他实验室的工作已经确定，II型蛋白分泌(T2S)是包括铜绿假单胞菌和嗜肺军团菌在内的肺部病原体毒力的主要促进剂。T2S分泌的蛋白质通常包括毒素和组织降解酶。因此，我们假设T2S在嗜麦芽窄食单胞菌的发病机制中起关键作用。为了测试这一点，我们将突变编码T2S装置的基因，这些基因已经通过嗜麦芽窄食单胞菌基因组测序而被揭示，然后在嗜麦芽窄食单胞菌肺部感染的小鼠模型中检查突变。突变体感染和/或损害肺部的能力的降低将引发对效应者的未来追求。其他过去的工作表明，IV型菌毛(T4P)促进肺部感染，最近的测序也表明嗜麦芽窄食单胞菌编码这种类型的表面附属物。因此，我们推测嗜麦芽窄食单胞菌的T4P是疾病的另一个促进剂。为了解决这个问题，我们将测试嗜麦芽窄食单胞菌的T4P突变体在小鼠肺中的行为。所获得的数据有可能导致新形式的传染病诊断、治疗或预防。公共卫生相关性：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、血液、心脏、尿路、中枢神经系统、眼睛、皮肤和软组织的感染。呼吸道是嗜麦芽窄食单胞菌最常见的部位，大约5%的医院获得性肺炎与细菌有关。然而，人们对嗜麦芽窄食单胞菌感染肺部的方式知之甚少。因此，这项拟议研究的目的是鉴定促进肺部感染的嗜麦芽窄食单胞菌因子，重点放在生物体的IV型菌毛和通过II型分泌系统分泌的蛋白质上。

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.