Antibiotic activities against S. aureus during P. aeruginosa co-infection
铜绿假单胞菌合并感染期间针对金黄色葡萄球菌的抗生素活性
基本信息
- 批准号:10318912
- 负责人:
- 金额:$ 38.47万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-01-01 至 2022-12-31
- 项目状态:已结题
- 来源:
- 关键词:AdjuvantAlginatesAminoglycoside resistanceAminoglycosidesAnaerobic BacteriaAntibiotic ResistanceAntibiotic TherapyAntibiotic susceptibilityAntibioticsBacteriaBacterial InfectionsBiological AssayCathetersCell Membrane PermeabilityCell WallChemosensitizationCiprofloxacinClinicClinicalComplexDataDevelopmentDropsEnvironmentEnzymesExhibitsFailureFluoroquinolonesFutureGenotypeGlycopeptidesGrowthImmunologic FactorsImplantInfectionLeadLength of StayMeasurementMeasuresMediatingMicrobial BiofilmsModelingMolecularMusNutrientOutcomeOxacillinOxidesOxygenPatientsPenetrationPeptidoglycanPhysiologicalPlayPopulationPredispositionProductionProton-Motive ForcePseudomonas aeruginosaPulmonary Cystic FibrosisQuantitative Reverse Transcriptase PCRRegulationReporterRespirationRoleStaphylococcus aureusTestingTobramycinTreatment FailureTreatment outcomeVancomycinWestern BlottingWorkantibiotic tolerancebactericidebeta-Lactamsburn modelburn woundclinically relevantclinically significantco-infectioncystic fibrosis patientsexperienceexperimental studyimprovedin vivomicroorganismmortalitymouse modelmutantnovelquorum sensingrhamnolipidsuccesssurfactantuptake
项目摘要
Summary Abstract
Predicting the efficacy of an antibiotic in a patient is a critical component of successfully treating infection.
Currently, there is an over-reliance on susceptibility assays involving pure bacterial cultures and controlled
growth conditions. These conditions are drastically different to those experienced by the bacteria during
infection. Hence, these assays fail to account for extrinsic factors that influence antibiotic susceptibility in the
infection environment. This contributes to unacceptable rates of treatment failure. Staphylococcus aureus is
responsible for numerous difficult-to-treat infections and antibiotic treatment failure is common. The
identification of novel extrinsic factors that significantly influence S. aureus antibiotic susceptibility in vivo will
greatly improve our ability to predict antibiotic efficacy in patients, leading to improved treatment outcomes.
These factors may include host interactions, nutrient and oxygen availability and interactions with other
microorganisms during polymicrobial infection.
Our preliminary studies demonstrate that P. aeruginosa produced molecules dramatically alter S.
aureus antibiotic susceptibility. We find the production of these molecules is highly variable among P.
aeruginosa clinical isolates. Preliminary experiments in mice suggest these interactions play an important role
in determining antibiotic efficacy in vivo.
We hypothesize that P. aeruginosa strongly influences S. aureus antibiotic susceptibility in patients
during polymicrobial infection.
In Aim 1, we propose to elucidate the molecular mechanisms responsible for this altered antibiotic efficacy.
Elucidation of these mechanisms will improve our understanding of S. aureus antibiotic tolerance and may also
lead to the development of novel adjuvants for the eradication of S. aureus populations.
In Aim 2, to determine the importance of P. aeruginosa/S. aureus interactions in patients, we will
examine clinical isolate pairs from burn and cystic fibrosis patients.
In Aim 3, to determine the relevance of these interactions during infection, we will examine antibiotic
efficacy against S. aureus mono-infection and during co-infection with P. aeruginosa using two complimentary
mouse models of infection.
Together, these experiments promise to reveal the role of bacterial interaction in determining the
outcome of antibiotic treatment of S. aureus. This will facilitate the future development of more sophisticated,
more accurate susceptibility determination and improved treatment outcomes in patients.
摘要
预测抗生素在患者中的疗效是成功治疗感染的关键组成部分。
目前,过度依赖于涉及纯细菌培养物和受控细菌培养物的敏感性测定。
生长条件这些条件与细菌在生长过程中所经历的条件截然不同。
感染因此,这些测定不能解释影响抗生素敏感性的外在因素,
感染环境。这导致了不可接受的治疗失败率。金黄色葡萄球菌是
导致许多难以治疗的感染和抗生素治疗失败是常见的。的
识别新的外在因素,显着影响S。体内金黄色葡萄球菌抗生素敏感性将
大大提高了我们预测患者抗生素疗效的能力,从而改善了治疗效果。
这些因素可能包括宿主相互作用、营养和氧气的可用性以及与其他环境的相互作用。
微生物在多微生物感染期间。
我们的初步研究表明,铜绿假单胞菌产生的分子显着改变S。
金黄色葡萄球菌抗生素敏感性我们发现,这些分子的生产是高度可变的P。
铜绿假单胞菌临床分离株在小鼠身上进行的初步实验表明,这些相互作用在
在体内测定抗生素的功效。
我们假设铜绿假单胞菌强烈影响S。患者对金黄色葡萄球菌抗生素的敏感性
在多微生物感染期间。
在目标1中,我们建议阐明这种改变抗生素疗效的分子机制。
阐明这些机制将有助于我们对S.金黄色葡萄球菌抗生素耐受性,也可能
导致开发用于根除S.金黄色葡萄球菌种群。
目的2:确定铜绿假单胞菌/S.金黄色葡萄球菌相互作用的患者,我们将
检查来自烧伤和囊性纤维化患者的临床分离物对。
在目标3中,为了确定感染期间这些相互作用的相关性,我们将研究抗生素
对S.金黄色葡萄球菌单一感染和在与铜绿假单胞菌共感染期间使用两个互补的
感染的小鼠模型。
总之,这些实验有望揭示细菌相互作用在决定细胞增殖中的作用。
抗生素治疗S.金黄色。这将有助于未来开发更先进,
更准确的易感性测定和改善患者的治疗结果。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Antibiotic-induced accumulation of lipid II synergizes with antimicrobial fatty acids to eradicate bacterial populations.
- DOI:10.7554/elife.80246
- 发表时间:2023-03-06
- 期刊:
- 影响因子:7.7
- 作者:Sidders AE;Kedziora KM;Arts M;Daniel JM;de Benedetti S;Beam JE;Bui DT;Parsons JB;Schneider T;Rowe SE;Conlon BP
- 通讯作者:Conlon BP
Harnessing ultrasound-stimulated phase change contrast agents to improve antibiotic efficacy against methicillin-resistant Staphylococcus aureus biofilms.
利用超声刺激的相位变化对比剂,以提高针对耐甲氧西林的金黄色葡萄球菌生物膜的抗生素疗效。
- DOI:10.1016/j.bioflm.2021.100049
- 发表时间:2021-12
- 期刊:
- 影响因子:6.8
- 作者:Durham PG;Sidders AE;Beam JE;Kedziora KM;Dayton PA;Conlon BP;Papadopoulou V;Rowe SE
- 通讯作者:Rowe SE
Antibiotic Tolerance and Treatment Outcomes in Cystic Fibrosis Methicillin-Resistant Staphylococcus aureus Infections.
- DOI:10.1128/spectrum.04061-22
- 发表时间:2023-02-14
- 期刊:
- 影响因子:3.7
- 作者:
- 通讯作者:
Persistent Methicillin-Resistant Staphylococcus aureus Bacteremia: Host, Pathogen, and Treatment.
- DOI:10.3390/antibiotics12030455
- 发表时间:2023-02-24
- 期刊:
- 影响因子:4.8
- 作者:Parsons, Joshua. B.;Westgeest, Annette. C.;Conlon, Brian. P. B.;Fowler, Vance. G., Jr.
- 通讯作者:Fowler, Vance. G., Jr.
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Brian Patrick Conlon其他文献
Brian Patrick Conlon的其他文献
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{{ truncateString('Brian Patrick Conlon', 18)}}的其他基金
The contribution of respiratory burst to antibiotic failure in Staphylococcus aureus bacteremia
呼吸爆发对金黄色葡萄球菌菌血症抗生素失效的影响
- 批准号:
10666777 - 财政年份:2022
- 资助金额:
$ 38.47万 - 项目类别:
Identifying the contribution of zinc limitation to antibiotic tolerance during S. aureus infection
确定金黄色葡萄球菌感染期间锌限制对抗生素耐受性的影响
- 批准号:
10192892 - 财政年份:2021
- 资助金额:
$ 38.47万 - 项目类别:
Antibiotic activities against S. aureus during P. aeruginosa co-infection
铜绿假单胞菌合并感染期间针对金黄色葡萄球菌的抗生素活性
- 批准号:
9917929 - 财政年份:2018
- 资助金额:
$ 38.47万 - 项目类别:
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