Targeting and Containing the Spread of VRSA

瞄准并遏制 VRSA 的传播

• 批准号: 8202949
• 负责人: Michael S Gilmore
• 金额: $ 29.12万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8202949
• 关键词: Abscess; Address; Affect; Antibiotic Resistance; Antibiotics; Antitoxins; Architecture; Biological; Caenorhabditis elegans; Chloramphenicol Resistance; Coculture Techniques; Communities; Community Hospitals; Complementarity Determining Regions; Containment; Development; Endophthalmitis; Enterococcus; Enterococcus faecalis; Environment; Epithelial Cells; Event; Exudate; Focal Infection; Genetic; Genome; Goals; Growth; Hospitals; Human; In Vitro; Infection; Instruction; Life; Maintenance; Metabolic; Methicillin Resistance; Microbe; Microbial Biofilms; Modeling; Multi-Drug Resistance; Mus; Nature; Nosocomial Infections; Partner in relationship; Pharmaceutical Preparations; Plasmids; Positioning Attribute; Property; Research; Resistance; ST5 gene; Staphylococcus aureus; Toxin; Vancomycin; Vancomycin Resistance; Vancomycin-resistant S. aureus; base; cost; fitness; in vitro Model; in vivo; killings; novel; programs; resistant strain; tool; trait; transmission process; vector; wound

PROJECT SUMMARY (See Instructions): Multidrug resistant Staphylococcus aureus (e.g., methicillin resistant [MRSA]) and enterococci (e.g., vancomycin resistant [VRE]) emerged in the 1960's and 1980's, and are leading causes of life-threatening infection in the hospital - more recently also in the community. Critically, after 20 years of containment, vancomycin resistance moved from VRE to MRSA, creating VRSA, and there are now 10 well documented cases. The overall goal of this program project is to identify and develop new drugs for treating infections caused by VRSA and VRE. This will be conducted hand-in-hand with studies to understand the development and proliferation of resistance in the multidrug resistant microbes being targeted in this Subproject. Overarching Goals: Determine what genetic or biological events led to the breach of containment of vancomycin resistance in VRE and transfer to VRSA, and demonstrate the activity of new compounds against them, by discovering and examining: -a known genetic event (insertional inactivation of a plasmid borne postsegregational killing TA module), - unknown traits within the genomes of the 10 well documented VRSA strains, and the putative VRE donors coisolated with them, - genetic and metabolic compatibilities, that may have predisposed them to coexist in mixed infection or participate in vancomycin resistance transfer, and - the efficacy of compounds developed in this PPG against these highly multidrug resistant, hospital adapted strains By understanding the basis for transfer as well as the nature of these increasingly resistant strains, we will be better positioned to assess the threat of continued erosion of antibiotic sensitivity in leading causes of hospital and community infection in the US, and will be alert to the types of conditions that promote this transfer.

项目总结（见说明）： 多重耐药金黄色葡萄球菌（例如，耐甲氧西林[MRSA]）和肠球菌（例如，万古霉素耐药[VRE]）出现于20世纪60年代和80年代，并且是医院中威胁生命的感染的主要原因-最近也在社区中。至关重要的是，经过20年的遏制，万古霉素耐药性从VRE转移到MRSA，创造了VRSA，现在有10个有据可查的病例。该计划项目的总体目标是确定和开发用于治疗VRSA和VRE引起的感染的新药。这将与研究携手进行，以了解该子项目中靶向的多药耐药微生物中耐药性的发展和扩散。 总体目标：确定哪些遗传或生物学事件导致VRE中万古霉素耐药性的遏制突破并转移到VRSA，并通过发现和检查证明新化合物对它们的活性： - 已知的遗传事件（质粒携带的分离后杀伤TA模块的插入失活）， - 在10个有据可查的VRSA菌株的基因组中存在未知性状， VRE供体与它们共隔离， - 遗传和代谢相容性，可能使它们在混合感染中共存或参与万古霉素耐药转移，以及 - 本PPG中开发的化合物对这些高度多药耐药的医院适应性菌株的疗效 通过了解转移的基础以及这些日益耐药的菌株的性质，我们将能够更好地评估美国医院和社区感染的主要原因中抗生素敏感性持续侵蚀的威胁，并对促进这种转移的条件类型保持警惕。