Genetic determinants of bacterial fitness in polymicrobial wound infections

多种微生物伤口感染中细菌适应性的遗传决定因素

基本信息

批准号：
8700960
负责人：
Marvin Whiteley
金额：
$ 24.16万
依托单位：
UNIVERSITY OF TEXAS AT AUSTIN
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-15 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8700960
关键词：
6H,8H-3,4-dihydropyrimido(4,5-c)(1,2)oxazin-7-one Acute Affect American Antibiotic Resistance Antibiotic Therapy Bacteria Bacterial Infections Burn injury Chronic Clinical Coculture Techniques Communities Decubitus ulcer Diabetic ulcer Exhibits Gene Expression Genes Genetic Genetic Determinism Genomics Goals Growth Healed Healthcare Systems High-Throughput Nucleotide Sequencing Hospitalization Human Infection Lead Metabolic Pathway Microbe Microbiology Modeling Molecular Mono-S Mus Organism Outcome Pathogenesis Pathway interactions Prevalence Process Protocols documentation Pseudomonas aeruginosa RNA Research Sampling Site Soft Tissue Infections Staphylococcus aureus Systemic infection Techniques Technology Therapeutic Virulence Wound Infection bacterial genetics base cost effective therapy fitness genome-wide healing in vivo insight knockout gene microbial mortality pathogen public health relevance transcriptomics wound

项目摘要

DESCRIPTION (provided by applicant): Most bacterial pathogenesis studies have focused on mono-culture infections; however, it is clear that many bacterial infections are not simply the result of colonization with a single species, but rather ensue from the action of polymicrobial communities. Microbes within polymicrobial infections often display synergistic interactions that result in enhanced colonization, persistence and antibiotic resistance in the infection site. Such interactions have been particularly noted in polymicrobial soft tissue infections, such as those in burns and chronic wounds, although the molecular processes controlling these synergistic interactions are generally not known. Studies elucidating the genetic pathways involved in polymicrobial interactions that contribute to enhanced persistence in vivo is critical for a comprehensive understanding of synergy, and a necessary first step towards developing therapeutics to treat multi-species infections. The overall goal of this research plan is to examine, from a genomic standpoint, how interactions between opportunistic pathogens impact in vivo persistence in acute and chronic wound infections. To accomplish this goal, high-throughput genomics techniques will be employed to identify microbial genes that are required for and expressed during polymicrobial synergy.

描述（由申请人提供）：大多数细菌发病机制研究都集中在单一培养物感染上；然而，很明显，许多细菌感染不仅仅是单一物种定植的结果，而是多种微生物群落作用的结果。多种微生物感染中的微生物通常表现出协同相互作用，导致感染部位的定植、持久性和抗生素耐药性增强。这种相互作用在多种微生物软组织感染中尤其明显，例如烧伤和慢性伤口，尽管控制这些协同相互作用的分子过程通常未知。研究阐明多微生物相互作用中涉及的遗传途径有助于增强体内持久性，这对于全面了解协同作用至关重要，也是开发治疗多物种感染的疗法的必要的第一步。该研究计划的总体目标是从基因组的角度检查机会病原体之间的相互作用如何影响急性和慢性伤口感染的体内持久性。为了实现这一目标，将采用高通量基因组学技术来鉴定多微生物协同作用所需和表达的微生物基因。