Potent antimicrobial peptides from carrion beetles

来自腐肉甲虫的有效抗菌肽

基本信息

批准号：
7671142
负责人：
Angelika Fath-Goodin
金额：
$ 11.83万
依托单位：
PARATECHS CORP.
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-03-16 至 2010-09-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7671142
关键词：
Antibiotic Resistance Antibiotics Anus Award Bacteria Biological Biological Preservation Biological Products Cadaver Caring Clinical Collaborations Complementary DNA Data Development Drosophila genus EST Library Engineering Environment Environmental Exposure Exhibits Expressed Sequence Tags Family Food Food Preservatives Funding Genes Genetic Genetic Materials Grant Growth Human Insect Proteins Insecta Laboratories Lead Length Literature Livestock Messenger RNA Methodology Microbe Microbial Antibiotic Resistance Modeling N-terminal Nature Nomenclature Oligonucleotide Primers Oral Order Coleoptera Organ Outcome Study Peptides Phase Phase I Clinical Trials Phase II Clinical Trials Planets Positioning Attribute Predisposition Process Property Proteins Public Health Qualifying Race Recombinant Proteins Reproduction Research Proposals Resistance Resistance development Resources Risk Salivary Septic Shock Source Specificity Structure Temperature Therapeutic Therapeutic Human Experimentation Time Tissues Transcript Two-Dimensional Gel Electrophoresis Upper arm Work antimicrobial antimicrobial drug antimicrobial peptide cDNA Library commercialization design drug development egg evaluation/testing expression vector feeding food resource fungus human disease microbial microbial genome mimetics model development novel pathogen pathogen exposure prevent protein expression public health relevance rapid growth research clinical testing resistant strain tool

项目摘要

DESCRIPTION (provided by applicant): Antibiotic resistant pathogenic microbes are responsible for thousands of human fatalities worldwide each year. The heightening risk of emerging pathogen resistance in clinical settings promotes the need for discovery and development of new antibiotics with a high degree of activity, potency, and specificity. ParaTechs Corporation has identified proteinaceous antimicrobial components in the anal and oral secretions of carrion beetles from the family Silphidae. These beetles reproduce by processing and/or burying carrion from vertebrate carcasses upon which they lay their eggs and rear their young. Preservation of the carcass is accomplished through constant covering of the carrion with substances aggressively secreted by the beetles. Carrion treated by the beetles in this manner has shown little evidence of microbial decay over extended periods of time. Here we demonstrate that potent antimicrobial activity is present in proteinaceous secretions from three Silphid species: Nicrophorus marginatus, Nicrophorus tomentosus, and Silpha (recently revised to Necrophila) americana. Our data demonstrate that proteins within the secretions have varying degrees of potency, specificity, and activity against bacterial growth suggesting that different antimicrobial components of the secretions may be acting synergistically preventing bacterial decomposition of the carrion. In this Phase I NIH:SBIR proposal we seek funding for the genetic and functional characterization of the potent antimicrobial components discovered in the oral and anal secretions of N. marginatus and S. americana for utilization as novel model antimicrobial molecules for clinical testing and biopharmaceutical applications. PUBLIC HEALTH RELEVANCE: The rapidly increasing microbial resistance to antibiotics in clinical settings is one of the world's most pressing public health concerns. The progressive emergence of new resistant pathogenic bacterial strains demands that efforts be undertaken to seek novel powerful antimicrobial agents that are effective against antibiotic resistant pathogen strains. The potent antimicrobial peptides to be isolated from carrion beetles and characterized with this award possess significant potential utility as novel biopharmaceuticals and may serve as functional models for the development of new and powerful antimicrobial drugs and human therapeutics.

描述（由申请人提供）：抗生素耐药的致病微生物每年造成数千人死亡。临床环境中新兴病原体抗性的风险增加促进了具有高度活性，效力和特异性的新抗生素的发现和开发的需求。 Paratechs Corporation已确定了来自家族的Silphidae牛肉甲虫的肛门和口服分泌物中的蛋白质抗菌成分。这些甲虫通过加工和/或从脊椎动物尸体中加工和/或埋葬腐肉来繁殖，它们产卵并饲养年轻。通过甲虫积极分泌的物质不断覆盖腐肉，可以保存尸体。甲虫以这种方式处理的腐肉显示很少有微生物衰变的证据。在这里，我们证明了来自三种Silphid物种的蛋白质分泌物中存在有效的抗菌活性：Nicrophorus Marginatus，Nicrophorus tomentosus和Silpha（最近被修订给Necrophila）Americana。我们的数据表明，分泌物中的蛋白质具有不同程度的效力，特异性和活性，可针对细菌生长，这表明分泌物的不同抗菌成分可能会协同预防腐肉的细菌分解。在这一阶段，NIH：SBIR提案，我们寻求资助资金，以供遗传和功能表征在Marginatus和Americana的口腔和肛门分泌物中发现的有效抗菌成分，作为用于临床测试和生物药物应用的新型模型抗菌分子的新型模型抗菌分子。公共卫生相关性：在临床环境中，对抗生素的迅速增加是世界上最紧迫的公共卫生问题之一。新的抗性致病细菌菌株的逐步出现要求努力寻求新型强大的抗微生物剂，这些抗生素耐药性病原体菌株有效。从腐肉甲虫中分离出来的有效抗菌肽并以该奖项为特征具有重要的潜在效用，作为新型的生物药物，并且可以作为开发新的和强大的抗菌药物和人类疗法的功能模型。