Potent antimicrobial peptides from carrion beetles

描述（由申请人提供）：抗生素耐药病原微生物每年导致全球数千人死亡。在临床环境中出现病原体耐药性的风险增加，促进了发现和开发具有高度活性、效力和特异性的新抗生素的需要。ParaTechs公司已经在食腐甲虫科的食腐甲虫的肛门和口腔分泌物中鉴定出蛋白质抗菌成分。这些甲虫通过加工和/或掩埋脊椎动物尸体上的腐肉来繁殖，并在腐肉上产卵和养育后代。尸体的保存是通过甲虫分泌的物质不断覆盖腐肉来实现的。甲虫以这种方式处理的腐肉在很长一段时间内几乎没有微生物腐烂的证据。在这里，我们表明，有效的抗菌活性是存在于蛋白质分泌物从三个Silphid物种：Nicrophorus marginatus，Nicrophorus tomentosus，和Silpha（最近修订为Necrophila）americana。我们的数据表明，分泌物内的蛋白质具有不同程度的效力，特异性和对细菌生长的活性，这表明分泌物的不同抗微生物组分可能协同作用，防止细菌分解腐肉。在第一阶段NIH：SBIR提案中，我们为在N. marginatus和S. Americana作为用于临床测试和生物制药应用的新型抗微生物分子模型。公共卫生相关性：临床环境中微生物对抗生素的耐药性迅速增加是世界上最紧迫的公共卫生问题之一。新的耐药性病原菌菌株的逐渐出现要求努力寻求有效对抗抗生素耐药性病原菌菌株的新型强效抗微生物剂。从腐肉甲虫中分离并获得该奖项的强效抗菌肽具有作为新型生物药物的重要潜在用途，并可作为开发新的强效抗菌药物和人类治疗药物的功能模型。

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.