Potent antimicrobial peptides from carrion beetles

来自腐肉甲虫的有效抗菌肽

• 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
• 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

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）：抗生素耐药性病原微生物每年导致全世界数千人死亡。临床环境中新出现的病原体耐药性风险不断增加，促进了对具有高度活性、效力和特异性的新型抗生素的发现和开发的需求。 ParaTechs 公司在食腐甲虫科腐肉甲虫的肛门和口腔分泌物中发现了蛋白质抗菌成分。这些甲虫通过加工和/或掩埋脊椎动物尸体的腐肉来繁殖，并在上面产卵并抚养幼崽。尸体的保存是通过用甲虫积极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几乎没有显示出微生物在长时间内腐烂的证据。在这里，我们证明了三种滑虫的蛋白质分泌物中存在有效的抗菌活性：Nicrophorus marginatus、Nicrophorus tomentosus 和 Silpha（最近修改为 Necrophila）americana。我们的数据表明，分泌物中的蛋白质对细菌生长具有不同程度的效力、特异性和活性，这表明分泌物的不同抗菌成分可能协同作用，防止腐肉的细菌分解。在这一第一阶段的 NIH:SBIR 提案中，我们寻求资金用于对在 N. marginatus 和 S. americana 的口腔和肛门分泌物中发现的有效抗菌成分进行遗传和功能表征，以用作临床测试和生物制药应用的新型抗菌分子模型。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。新的耐药病原菌菌株的不断出现要求努力寻找能够有效对抗抗生素耐药病原菌菌株的新型强效抗菌剂。从腐肉甲虫中分离出来并获得该奖项的强效抗菌肽具有作为新型生物制药的巨大潜在用途，并且可以作为开发新型强效抗菌药物和人类疗法的功能模型。