Potent antimicrobial peptides from carrion beetles

描述(申请人提供)：抗药性病原微生物每年在全球范围内造成数千人死亡。临床环境中新出现的病原体耐药性风险的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公司已经在鹿科腐肉甲虫的肛门和口腔分泌物中发现了蛋白质类抗菌成分。这些甲虫通过加工和/或埋葬脊椎动物身体上的腐肉来繁殖，它们在上面产卵并抚养后代。身体的保存是通过不断地用甲虫积极分泌的物质覆盖腐肉来完成的。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，我们证明了强大的抗菌活性存在于三个丝虫物种的蛋白质分泌物中：边缘丝虫、毛刺丝虫和美洲丝虫的Silpha(最近修改为NecroPhila)。我们的数据表明，分泌物中的蛋白质具有不同程度的效力、特异性和抗细菌生长的活性，这表明分泌物中的不同抗菌成分可能协同作用，防止腐肉的细菌分解。在这项第一阶段的NIH：SBIR提案中，我们寻求资金，用于在口腔和肛门分泌物中发现的有效抗菌成分的遗传和功能表征，以用作临床测试和生物制药应用的新型模型抗菌分子。与公共卫生相关：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。新的耐药病原菌的不断出现要求人们努力寻找新的有效的抗菌剂，以有效地对抗耐药病原菌。将从腐烂甲虫中分离出并以该奖项为特征的有效抗菌肽具有作为新型生物制药的重大潜在用途，并可能作为开发新的和强大的抗菌药物和人类疗法的功能模型。

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.