Proline uptake in staphylococcus aureus pathogenesis

金黄色葡萄球菌发病机制中的脯氨酸摄取

• 批准号: 6455861
• 负责人: WILLIAM R SCHWAN
• 金额: $ 12.9万
• 依托单位: UNIVERSITY OF WISCONSIN LA CROSSE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6455861
• 关键词: Staphylococcus aureus; Staphylococcus infection; aminoacid transport; bacteria infection mechanism; bacterial genetics; fusion gene; gene mutation; genetic promoter element; genetic recombination; genetic regulation; genetic strain; genetic transcription; genetic transduction; host organism interaction; laboratory mouse; molecular cloning; permease; plasmids; proline; protein sequence; protein structure function; transfection /expression vector; transport proteins; transposon /insertion element

Staphylococcus aureus is a significant human pathogen, which is the leading cause of surgical-wound infections and the second most frequent cause of nosocomial bloodstream infections in the United States. A significant number of cases of food poisoning are also linked to contamination of foodstuffs with S. aureus. Almost every tissue and organ within the human body is susceptible to infections by this species. Many of the current infections are caused by staphylococcal strains that are resistant to one or more antibiotics. Eighty to ninety percent of all S. aureus strains are resistant to the antibiotic penicillin and up to fifty percent of all strains isolated from patients in hospitals are resistant to methicillin. Recent outbreaks of community-acquired S. aureus possessing methicillin resistance and the emergence of vancomycin-resistant S. aureus strains mean that some strains may be untreatable by any antibiotic. Because S. aureus is able to infect so many different tissues within the human body, this grant proposes to study proline transport in S. aureus as a means to study the role proline transporters play in the pathogenesis of the bacteria. At least two proline transport systems are known for S. aureus. This grant proposes to identify the homolog of the ProP low affinity proline transporter and mutate the prop gene by allelic exchange or transposon mutagenesis with Tn917. With this proP mutant, a proPputP double mutant will then be created. Both the single and double mutants will be tested for proline transport differences in vitro and for their attenuation in animal models of infection. The regulation of the high affinity proline transport gene, putP, also will be tested in vitro in proline uptake assays and in vivo in several animal models of infection using a putP transcriptional fusion. The results of this study will help us understand the role of proline transport in S. aureus infections.

金黄色葡萄球菌是一种重要的人类病原体，是美国伤口感染的主要原因，也是医院血流感染的第二大常见原因。大量的食物中毒病例也与食品中的沙门氏菌污染有关。金黄色。几乎人体内的每一个组织和器官都容易受到该物种的感染。目前的许多感染是由对一种或多种抗生素具有耐药性的葡萄球菌菌株引起的。百分之八十到九十的S。金黄色葡萄球菌菌株对抗生素青霉素具有抗性，并且从医院中的患者分离的所有菌株中高达50%对甲氧西林具有抗性。最近爆发的社区获得性S。金黄色葡萄球菌对甲氧西林耐药，万古霉素耐药的出现。金黄色葡萄球菌菌株意味着某些菌株可能无法用任何抗生素治疗。因为S.金黄色葡萄球菌能够感染人体内许多不同的组织，因此该资助计划研究金黄色葡萄球菌中的脯氨酸转运。金黄色葡萄球菌作为一种手段，研究脯氨酸转运蛋白在细菌的发病机制中发挥的作用。已知S.金黄色。该基金拟鉴定ProP低亲和力脯氨酸转运蛋白的同源物，并通过与Tn917的等位基因交换或转座子诱变来突变prop基因。有了这个proP突变体，将产生proPputP双突变体。将测试单突变体和双突变体的体外脯氨酸转运差异以及它们在感染动物模型中的衰减。高亲和力脯氨酸转运基因putP的调节也将在脯氨酸摄取测定中在体外进行测试，并使用putP转录融合在几种动物感染模型中进行体内测试。本研究结果有助于我们了解脯氨酸转运在S.金黄色葡萄球菌感染

项目成果

Flagella allow uropathogenic Escherichia coli ascension into murine kidneys.

鞭毛允许尿路致病性大肠杆菌上升到小鼠肾脏。

• DOI: 10.1016/j.ijmm.2007.05.009
• 发表时间: 2008
• 期刊: International journal of medical microbiology : IJMM
• 作者: Schwan,WilliamR

Mutations in the cueA gene encoding a copper homeostasis P-type ATPase reduce the pathogenicity of Pseudomonas aeruginosa in mice.

• DOI: 10.1016/j.ijmm.2005.05.005
• 发表时间: 2005-08
• 期刊: International journal of medical microbiology : IJMM
• 作者: W. Schwan;P. Warrener;Elizabeth Keunz;C. Stover;K. Folger

Osmolyte transport in Staphylococcus aureus and the role in pathogenesis.

金黄色葡萄球菌中渗透剂的转运及其在发病机制中的作用。

• DOI: 10.5495/wjcid.v6.i2.22
• 发表时间: 2016
• 期刊: World journal of clinical infectious diseases
• 作者: Schwan,WilliamR;Wetzel,KeithJ
• 通讯作者: Wetzel,KeithJ

Down-regulation of the kps region 1 capsular assembly operon following attachment of Escherichia coli type 1 fimbriae to D-mannose receptors.

1 型大肠杆菌菌毛附着至 D-甘露糖受体后，kps 区域 1 荚膜组装操纵子下调。

• DOI: 10.1128/iai.73.2.1226-1231.2005
• 发表时间: 2005
• 期刊: Infection and immunity
• 影响因子: 3.1
• 作者: Schwan,WilliamR;Beck,MichaelT;Hultgren,ScottJ;Pinkner,Jerry;Woolever,NathanL;Larson,Thomas
• 通讯作者: Larson,Thomas

Management of methicillin-resistant Staphylococcus aureus mediated ventilator-associated pneumonia.

耐甲氧西林金黄色葡萄球菌介导的呼吸机相关性肺炎的治疗。

• 发表时间: 2018
• 期刊: Current trends in microbiology
• 作者: Dahal,Manisha;Schwan,WilliamR
• 通讯作者: Schwan,WilliamR