Staphylococcus Biology in Ocular Infections
眼部感染中的葡萄球菌生物学
基本信息
- 批准号:10672933
- 负责人:
- 金额:$ 36.25万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-09-01 至 2026-07-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAdherenceAdhesionsAgonistAnimalsAnti-Inflammatory AgentsAntibiotic ResistanceAntibioticsAreaAttentionBacteriaBacterial AdhesinsBacterial Eye InfectionsBacterial InfectionsBindingBiologyBlindnessBlood-Retinal BarrierBypassCell Culture TechniquesCell LineCellsCommunicable DiseasesCorneaDataDevelopmentDiseaseEndophthalmitisEquationEventExperimental DesignsEyeEye InfectionsFutureGenesGenus staphylococcusGoalsGrowthHealthImmuneImmune responseImmune systemImmunityIn VitroInfectionInfection preventionInflammationInflammatoryInflammatory ResponseInvadedKeratitisKnowledgeMediatingModelingMorbidity - disease rateMulti-Drug ResistanceOrganismPainPathogenesisPathogenicityPathway interactionsPatient-Focused OutcomesPatientsPositioning AttributePreventionProcessProductionPublishingRegulationResearchResistanceRetinaRiskSpeedStaphylococcus aureusStrategic PlanningSurfaceTestingTherapeuticTimeTissuesToxinVirulenceVirulence FactorsVisionVisualcorneal epitheliumdesignimprovedin vivoineffective therapiesinnate immune pathwaysinnovationleukotoxinmethicillin resistant Staphylococcus aureusmutantnegative affectpreservationpreventprogramsresponseretinal damagetherapeutic developmenttherapeutic target
项目摘要
PROJECT SUMMARY / ABSTRACT
Bacterial eye infections cause a significant number of cases of blindness worldwide. Staphylococcus
aureus causes a majority of these infections of the cornea (keratitis) and interior of the eye (endophthal-
mitis). S. aureus produces several adhesins on its surface which aid in tissue attachment, surface components
which trigger innate immune pathways and inflammation, and toxins which disrupt barriers and kill immune
cells. The coordinated synthesis of these virulence factors aids the organism in host survival, and the host is
usually negatively affected. In the eye, this can manifest as a painfully damaged cornea or irreversibly
damaged retina, resulting in significant vision loss. To make matters worse, S. aureus is considered a Serious
Threat on the CDC’s list of Antibiotic Resistance Threats in the US. MRSA and multidrug resistance are now
common in ocular isolates, elevating the risk of ocular infections that are difficult to treat.
We and others have investigated the pathogenic mechanisms underlying ocular bacterial infections. For
S. aureus, animal infection models and ocular cell lines have been used to investigate the areas noted above.
We have a very good idea of which toxins damage the cornea and retina and which innate pathways are
involved in corneal and intraocular inflammation. This proposal is focused on the factors involved in the
earliest events in S. aureus ocular infections, events that, to date, have drawn minimal attention.
This new R01 proposal is based on the global hypothesis that coordinated regulation of S. aureus
adhesins and toxins facilitate adherence to tissue, barrier breach, and escape from the acute immune
response. The scientific premise is based on preliminary and published data demonstrating that: 1) adhesins
on the S. aureus surface, when absent, reduce adhesion to corneal cells, 2) leukotoxins, when absent, reduce
virulence in keratitis and endophthalmitis, and 3) S. aureus breach of the blood-retina barrier appears to be
adhesin- and toxin-mediated. These areas are investigated in three separate but related aims focused on early
events in S. aureus keratitis and endophthalmitis. We will use well-characterized S. aureus virulence factor-
defective mutants and feasible in vitro and in vivo infection models in rigorous and straightforward experiments
designed to define the S. aureus factors important in these events.
For patients with eye infections, ineffective treatment often equates with vision loss. Our approaches to
addressing these gaps in our field are innovative, translationally relevant, and will move the ocular infectious
disease field forward by identifying the S. aureus factors responsible for adhesion to tissue and circumvention
of the acute response, possibly uncovering targets that lead to more rational use or development of
therapeutics for prevention and treatment of infection. These studies are a logical extension of our ocular
infection research program, and we are well positioned to contribute new and important information that will
improve options for preventing infection and preserving vision.
项目摘要/摘要
细菌性眼部感染在全球范围内导致相当数量的失明病例。葡萄球菌
金黄色葡萄球菌引起的角膜感染(角膜炎)和眼内感染(眼内感染)占大多数。
Mitis)。金黄色葡萄球菌在其表面产生几种粘附素,有助于组织附着、表面成分
引发先天免疫途径和炎症,以及破坏屏障并杀死免疫力的毒素
细胞。这些毒力因子的协调合成有助于有机体的生存,宿主是
通常会受到负面影响。在眼睛中,这可能表现为痛苦的角膜损伤或不可逆转。
视网膜受损,导致严重的视力丧失。更糟糕的是,金黄色葡萄球菌被认为是一种严重的
在美国疾病控制与预防中心的抗生素耐药性威胁名单上。MRSA和多药耐药现在
在眼部隔离中很常见,增加了难以治疗的眼部感染的风险。
我们和其他人研究了眼部细菌感染的致病机制。为
利用金黄色葡萄球菌、动物感染模型和眼细胞系对上述区域进行了研究。
我们非常清楚哪些毒素会损害角膜和视网膜,哪些是先天途径
与角膜和眼内炎症有关。这项建议的重点是
金黄色葡萄球菌眼部感染的最早事件,到目前为止,引起关注的事件很少。
这一新的R01提案基于全球假说,即金黄色葡萄球菌的协调调节
粘附素和毒素有助于粘连组织、突破屏障和逃避急性免疫。
回应。科学前提是基于初步的和已发表的数据表明:1)粘附素
在金黄色葡萄球菌表面,当缺乏时,减少与角膜细胞的黏附;2)白细胞毒素,当缺乏时,减少
角膜炎和眼内炎的毒性,以及3)金黄色葡萄球菌突破血-视网膜屏障似乎是
粘附素和毒素介导的。这些领域在三个独立但相关的目标中进行调查,重点放在早期
金黄色葡萄球菌角膜炎和眼内炎事件。我们将使用金黄色葡萄球菌的毒力因子-
严格和直接实验中的缺陷突变体和可行的体外和体内感染模型
旨在定义在这些事件中重要的金黄色葡萄球菌因素。
对于眼部感染的患者,无效的治疗通常等同于视力丧失。我们的方法是
解决我们领域的这些差距是创新的,具有翻译相关性,并将推动眼部感染
通过识别导致组织粘连和规避的金黄色葡萄球菌因子向前推进疾病领域
可能会发现导致更合理地使用或发展
预防和治疗感染的治疗学。这些研究是我们眼睛的合理延伸
感染研究计划,我们处于有利地位,将贡献新的重要信息
改进预防感染和保护视力的选择。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ocular Bacterial Infections: A Ten-Year Survey and Review of Causative Organisms Based on the Oklahoma Experience.
- DOI:10.3390/microorganisms11071802
- 发表时间:2023-07-13
- 期刊:
- 影响因子:4.5
- 作者:
- 通讯作者:
The Role of C-X-C Chemokines in Staphylococcus aureus Endophthalmitis.
- DOI:10.1167/iovs.64.3.10
- 发表时间:2023-03-01
- 期刊:
- 影响因子:4.4
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Michelle C Callegan其他文献
Michelle C Callegan的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Michelle C Callegan', 18)}}的其他基金
Pathogenic Mechanisms of Bacillus Endophthalmitis
芽孢杆菌眼内炎的致病机制
- 批准号:
10178032 - 财政年份:2018
- 资助金额:
$ 36.25万 - 项目类别:
Pathogenic Mechanisms of Bacillus Endophthalmitis
芽孢杆菌眼内炎的致病机制
- 批准号:
9759927 - 财政年份:2018
- 资助金额:
$ 36.25万 - 项目类别:
Pathogenic Mechanisms of Bacillus Endophthalmitis
芽孢杆菌眼内炎的致病机制
- 批准号:
10428514 - 财政年份:2018
- 资助金额:
$ 36.25万 - 项目类别:
相似海外基金
Pharmacy-led Transitions of Care Intervention to Address System-Level Barriers and Improve Medication Adherence in Socioeconomically Disadvantaged Populations
药房主导的护理干预转型,以解决系统层面的障碍并提高社会经济弱势群体的药物依从性
- 批准号:
10594350 - 财政年份:2023
- 资助金额:
$ 36.25万 - 项目类别:
Evaluating Centralizing Interventions to Address Low Adherence to Lung Cancer Screening Follow-up in Decentralized Settings
评估集中干预措施,以解决分散环境中肺癌筛查随访依从性低的问题
- 批准号:
10738120 - 财政年份:2023
- 资助金额:
$ 36.25万 - 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
- 批准号:
10526768 - 财政年份:2022
- 资助金额:
$ 36.25万 - 项目类别:
Suubi-Mhealth: A mobile health intervention to address depression and improve ART adherence among Youth living with HIV (YLHIV) in Uganda
Suubi-Mhealth:一种移动健康干预措施,旨在解决乌干达艾滋病毒感染者 (YLHIV) 青少年的抑郁症问题并提高抗逆转录病毒疗法的依从性
- 批准号:
10701072 - 财政年份:2022
- 资助金额:
$ 36.25万 - 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
- 批准号:
10679092 - 财政年份:2021
- 资助金额:
$ 36.25万 - 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
- 批准号:
10432133 - 财政年份:2021
- 资助金额:
$ 36.25万 - 项目类别:
A behavioral intervention for Black men who have sex with men and live with HIV to address intersectional stigma and improve antiretroviral therapy adherence
针对男男性行为且感染艾滋病毒的黑人男性进行行为干预,以解决交叉耻辱并提高抗逆转录病毒治疗的依从性
- 批准号:
10327065 - 财政年份:2021
- 资助金额:
$ 36.25万 - 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
- 批准号:
10377366 - 财政年份:2019
- 资助金额:
$ 36.25万 - 项目类别:
Leveraging Technology to Address Access and Adherence to Conventional Hospital-Based Pulmonary Rehabilitation in Veterans with COPD
利用技术解决慢性阻塞性肺病退伍军人接受和坚持传统医院肺康复的问题
- 批准号:
10574496 - 财政年份:2019
- 资助金额:
$ 36.25万 - 项目类别:
Targeted interventions to address the multi-level effects of gender-based violence on PrEP uptake and adherence among adolescent girls and young women in Kenya
有针对性的干预措施,以解决性别暴力对肯尼亚少女和年轻妇女接受和坚持 PrEP 的多层面影响
- 批准号:
9403567 - 财政年份:2017
- 资助金额:
$ 36.25万 - 项目类别:














{{item.name}}会员




