Regulation of stress resistance and virulence genes in Acinetobacter baumannii

鲍曼不动杆菌抗逆性和毒力基因的调控

• 批准号: 9098590
• 负责人: HOWARD A SHUMAN
• 金额: $ 19.19万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9098590
• 关键词: Acinetobacter baumannii; Aerobic; Bacteria; Bacterial Outer Membrane Proteins; Cessation of life; Community-Acquired Infections; Complement; DNA Insertion Elements; DNA-Binding Proteins; Deletion Mutation; Disease; Endocarditis; Environment; Exhibits; Frequencies; Gene Deletion; Gene Expression; Genes; Genetic; Genetic Screening; Genome; Growth; Health; Healthcare; Hemolymph; Hospitals; Human; Infection; Infectious Agent; Insecta; Insertion Mutation; Intervention; Iron; Knowledge; Larva; Ligase; Measures; Membrane Proteins; Microbial Biofilms; Modeling; Molecular; Moths; Multi-Drug Resistance; Nosocomial Infections; Nutrient; Organism; Osteomyelitis; Oxidative Stress; Pain; Pathogenesis; Phenotype; Pneumonia; Polysaccharides; Potassium Channel; Prevalence; Production; Protein Secretion; Proteins; Regulation; Regulator Genes; Regulatory Pathway; Reporting; Resistance; Sepsis; Siderophores; Site; Skin Tissue; Soft Tissue Infections; Source; Stress; System; Testing; Toxin; Transcriptional Regulation; Trehalose; Urinary tract infection; Virulence; Virulence Factors; Waxes; Work; Zinc; base; biological adaptation to stress; genetic regulatory protein; mutant; pathogen; resistant strain; transcriptome; transcriptome sequencing

 DESCRIPTION (provided by applicant): Acinetobacter baumannii is a strictly aerobic, gram-negative coccobacillus that has recently emerged as a significant opportunistic human pathogen. This organism is most commonly associated with nosocomial infections and is generally considered to be an opportunistic human pathogen, although some community acquired infections are reported. Diseases caused by A. baumannii include skin and soft tissue infections, infections of the urinary tract, as well as more invasive diseases such as endocarditis, sepsis, osteomyelitis and pneumonia. A. baumannii infections are further complicated by the increasing prevalence of multidrug resistant (MDR) strains. At present, little is known about A. baumannii virulence mechanisms. Currently proposed virulence determinants include the production of siderophores, elaboration of capsular polysaccharides, biofilm production, the bacterial outer membrane protein A (OmpA), as well as several other candidate proteins of unknown function. There is even less information about how virulence-related genes are regulated. To discover A. baumannii virulence genes, we took advantage of an invertebrate insect model that has been used to study a variety of infectious agents, the larva of the wax moth, Galleria mellonella. We conducted a forward genetic screen using a large pool of transposon insertion mutations in the genome of a MDR pathogenic strain of A. baumannii, AB5075. By sequencing the insertion sites of the transposons in bacteria grown in rich media and from infected larvae, we identified more than 180 genes that appear to be specifically required for survival in larvae and dispensable for survival and growth in rich media. Seventeen of the genes encode products that are annotated as either DNA binding proteins or other types of regulatory proteins. In addition, 11 genes predicted to encode proteins related to resistance to osmotic stress were found. We created deletions of the genes annotated as trehalose synthetase (otsB), potassium channels (trkAH), and a mechanosensitive channel (mscS). These mutants also exhibited decreased survival in larva hemolymph compared to wild-type A. baumannii AB5075. This proposed work includes construction of deletion mutations of the 28 genes (17 regulators and 11 stress resistance) and testing their phenotypes in the Galleria model. The ability of the corresponding wild-type genes to complement mutants that exhibit a phenotype will be evaluated. Transcriptional profiling by RNAseq will be performed on several mutants that exhibit decreased virulence in the Galleria larva model. This work will result in important new knowledge about the genetic basis of virulence in an emerging human pathogen.

 描述（由申请人提供）：鲍曼不动杆菌是一种严格需氧的革兰氏阴性球杆菌，最近已成为一种重要的机会性人类病原体，尽管这种生物体最常与医院感染相关，并且通常被认为是一种机会性人类病原体。据报道，鲍曼不动杆菌引起的一些社区获得性感染包括皮肤和软组织感染、泌尿道感染。心内膜炎、败血症、骨髓炎和肺炎等更多侵袭性疾病因多重耐药（MDR）菌株的流行而变得更加复杂。目前，人们对鲍曼不动杆菌的毒力机制知之甚少。铁载体的产生、荚膜多糖的精制、生物膜的产生、细菌外膜蛋白 A (OmpA) 以及其他几种候选蛋白为了发现鲍曼不动杆菌的毒力基因，我们利用了一种无脊椎动物模型，该模型已被用于研究各种传染原，即鲍曼不动杆菌的幼虫。我们利用鲍曼不动杆菌 (A. baumannii) 的 MDR 致病菌株 AB5075 基因组中的大量转座子插入突变进行了正向遗传筛选。通过对在丰富培养基中生长的细菌和受感染幼虫中转座子的插入位点进行分析，我们鉴定了 180 多个基因，这些基因似乎是幼虫生存所必需的，并且对于在丰富培养基中的生存和生长来说是可有可无的，其中 17 个基因编码的产物。被注释为 DNA 结合蛋白或其他类型的调节蛋白。此外，预计有 11 个基因编码与抗性相关的蛋白。 我们发现了海藻糖合成酶 (otsB)、钾通道 (trkAH) 和机械敏感通道 (mscS) 基因的缺失，与野生型鲍曼不动杆菌相比，这些突变体在幼虫血淋巴中的存活率也降低。 AB5075。这项拟议的工作包括构建 28 个基因（17 个调节基因和 11 个抗逆基因）的缺失突变并测试它们的表型。在 Galleria 幼虫模型中，相应的野生型基因与表现出表型的突变体互补的能力将会降低。关于新兴人类病原体毒力遗传基础的新知识。

项目成果

GigC, a LysR Family Transcription Regulator, Is Required for Cysteine Metabolism and Virulence in Acinetobacter baumannii.

GigC 是一种 LysR 家族转录调节因子，是鲍曼不动杆菌半胱氨酸代谢和毒力所必需的。

• 发表时间: 2020
• 影响因子: 3.1
• 作者: Gebhardt, Michael J;Czyz, Daniel M;Singh, Shweta;Zurawski, Daniel V;Becker, Lev;Shuman, Howard A
• 通讯作者: Shuman, Howard A

Joint Transcriptional Control of Virulence and Resistance to Antibiotic and Environmental Stress in Acinetobacter baumannii.

鲍曼不动杆菌毒力和抗生素及环境应激抗性的联合转录控制。

• 发表时间: 2015-11-10
• 影响因子: 6.4
• 作者: Gebhardt, Michael J;Gallagher, Larry A;Jacobson, Rachael K;Usacheva, Elena A;Peterson, Lance R;Zurawski, Daniel V;Shuman, Howard A
• 通讯作者: Shuman, Howard A

Optimizing tick artificial membrane feeding for Ixodes scapularis.

优化肩胛硬蜱的蜱人工膜喂养。

• 发表时间: 2023-09-27
• 影响因子: 4.6
• 作者: Guizzo, Melina Garcia;Meneses, Claudio;Cecilio, Pedro Amado;Alvarenga, Patricia Hessab;Sonenshine, Daniel;Ribeiro, Jose M.
• 通讯作者: Ribeiro, Jose M.

GigA and GigB are Master Regulators of Antibiotic Resistance, Stress Responses, and Virulence in Acinetobacter baumannii.

GigA 和 GigB 是鲍曼不动杆菌抗生素耐药性、应激反应和毒力的主要调节因子。

• 发表时间: 2017-05-15
• 影响因子: 3.2
• 作者: Gebhardt, Michael J;Shuman, Howard A
• 通讯作者: Shuman, Howard A

Molecular Diversity between Salivary Proteins from New World and Old World Sand Flies with Emphasis on Bichromomyia olmeca, the Sand Fly Vector of Leishmania mexicana in Mesoamerica.

新世界和旧世界沙蝇唾液蛋白之间的分子多样性，重点是中美洲墨西哥利什曼原虫的沙蝇媒介奥尔美卡双色蝇。

• 发表时间: 2016
• 影响因子: 3.8
• 作者: Abdeladhim, Maha;V Coutinho;Townsend, Shannon;Pasos;Sanchez, Laura;Rasouli, Manoochehr;B Guimaraes;Aslan, Hamide;Francischetti, Ivo M B;Oliveira, Fabiano;Becker, Ingeborg;Kamhawi, Shaden;Ribeiro, Jos
• 通讯作者: Ribeiro, Jos