CRYPTOCOCCUS NEOFORMANS--OXIDATIVE KILLING MECHANISMS

新型隐球菌——氧化杀伤机制

• 批准号: 6373716
• 负责人: VISHNU CHATURVEDI
• 金额: $ 11.37万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-09-01 至 2004-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6373716
• 关键词: Cryptococcus neoformans; antioxidants; electron spin resonance spectroscopy; gene mutation; genetic strain; host organism interaction; human tissue; laboratory mouse; mannitol; melanins; microorganism immunology; molecular cloning; monocyte; neutrophil; oxidation

DESCRIPTION: (Adapted from Applicant's Abstract) Cryptococcus neoformans causes serious opportunistic disease in patients with AIDS and hematologic malignancies. Phagocytes provide first line of defense against this fungus whereas cell-mediated immunity controls the fungus during systemic disease. It is believed that general defects in monocyte and neutrophil functions combined with impaired T cell responses predispose HIV patients to cryptococcosis. However, it is not know how human phagocytes oxidatively kill C. neoformans and how the fungus foils such attacks. Also, preliminary observations suggest that a distal neutrophil oxidant is fungicidal and that fungal mannitol may protect from oxidative killing. Therefore, the central hypotheses to be tested in this project are: (1) that oxidants distal to superoxide anion (O2-) and hydrogen peroxide (H2O2) are critical in C. neoformans killing and (2) that cryptococcal mannitol acts as an antioxidant. In Specific Aim 1, the investigator will study oxidative killing mechanisms of human monocytes and neutrophils against C. neoformans to identify fungicidal oxidants that may include hydroxyl radicals, hypochlorite, and/or nitric oxide. Specific Aim 2 is to determine whether C. neoformans mannitol functions as an antioxidant in leukocyte interactions by employing C. neoformans natural isolates, mutants deleted in mannitol or over-expressing mannitol. Specific Aim 3 is to compare mannitol with cryptococcal melanin for their antioxidant functions. Mannitol +/- features will be introduced into melanin +/- strains for comparison in oxidant assays. These studies are significant because they will i) characterize leukocyte oxidants that are fungicidal for C. neoformans, ii) define the antioxidant role of C. neoformans mannitol, iii) examine mannitol vis a vis melanin as an antioxidant, iv) suggest unique targets for developing antifungals, and iv) provide methodological basis to study phagocyte oxidants against other pathogenic fungi.

描述：（改编自申请人的摘要）新型隐球菌 导致艾滋病和血液病患者发生严重的机会性疾病 恶性肿瘤。 吞噬细胞提供了针对这种真菌的第一道防线 而细胞介导的免疫在全身性疾病期间控制真菌。 人们认为单核细胞和中性粒细胞功能的一般缺陷 加上 T 细胞反应受损，HIV 患者容易出现 隐球菌病。 然而，目前尚不清楚人类吞噬细胞如何氧化 杀死新型隐球菌以及该真菌如何挫败此类攻击。 另外，初步 观察结果表明，远端中性粒细胞氧化剂具有杀菌作用，并且 甘露醇可以防止真菌被氧化杀死。 因此，中央 本项目要检验的假设是：（1）氧化剂远离 超氧阴离子 (O2-) 和过氧化氢 (H2O2) 在 C 中至关重要。 新型隐球菌杀灭和 (2) 隐球菌甘露醇充当 抗氧化剂。 在具体目标 1 中，研究者将研究氧化 人单核细胞和中性粒细胞对新型隐球菌的杀伤机制 识别可能包括羟基自由基的杀菌氧化剂， 次氯酸盐和/或一氧化氮。 具体目标 2 是确定是否 C.新型隐球菌甘露醇在白细胞相互作用中充当抗氧化剂 通过使用新型隐球菌天然分离物、在甘露醇中删除的突变体或 过度表达甘露醇。 具体目标 3 是将甘露醇与 隐球菌黑色素具有抗氧化功能。 甘露醇 +/- 特性 将被引入黑色素+/-菌株中以进行氧化剂比较 化验。 这些研究意义重大，因为它们将 i) 描述 对新型隐球菌具有杀菌作用的白细胞氧化剂，ii) 定义 新型隐球菌甘露醇的抗氧化作用，iii) 对比甘露醇进行检查 黑色素作为一种抗氧化剂，iv) 建议开发独特的目标 抗真菌药物，以及 iv) 为研究吞噬细胞提供方法学基础 对抗其他病原真菌的氧化剂。

项目成果

Cryptococcus gattii in AIDS patients, southern California.

• DOI: 10.3201/eid1111.040875
• 发表时间: 2005-11
• 期刊: Emerging infectious diseases
• 影响因子: 11.8
• 作者: Chaturvedi S;Dyavaiah M;Larsen RA;Chaturvedi V
• 通讯作者: Chaturvedi V

Molecular cloning, phylogenetic analysis and three-dimensional modeling of Cu,Zn superoxide dismutase (CnSOD1) from three varieties of Cryptococcus neoformans.

• DOI: 10.1016/s0378-1119(01)00408-5
• 发表时间: 2001-05
• 期刊: Gene
• 影响因子: 3.5
• 作者: S. Chaturvedi;Andrew Hamilton;Paul Hobby;Guan Zhu;Charles V. Lowry;Vishnu Chaturvedi;Vishnu Chaturvedi;Vishnu Chaturvedi

Cryptococcus gattii: a resurgent fungal pathogen.

• DOI: 10.1016/j.tim.2011.07.010
• 发表时间: 2011-11
• 期刊: TRENDS IN MICROBIOLOGY
• 影响因子: 15.9
• 作者: Chaturvedi, Vishnu;Chaturvedi, Sudha
• 通讯作者: Chaturvedi, Sudha