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Antimicrobial peptide resistance in Campylobacter jejuni

空肠弯曲杆菌的抗菌肽耐药性

基本信息

批准号：
7914369
负责人：
JUN LIN
金额：
$ 16.56万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
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：
2009-08-15 至 2012-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7914369
关键词：
Animals Antibiotics Antimicrobial Resistance Bacteria Bacterial Infections Biochemical Biological Models Campylobacter Campylobacter coli Campylobacter infection Campylobacter jejuni Candidate Disease Gene Chickens Clinical Complex Defensins Development Domestic Fowls Exposure to Farming environment Food Safety Gastroenteritis Gene Silencing Genes Genetic Genome Goals Growth Host Defense Human In Vitro Intervention Intestines Knowledge Lead Meat Molecular Mutagenesis Natural Immunity Peptide Antibiotics Peptides Polymyxin B Population Predisposition Prevalence Public Health Research Resistance Resistance development Role Source Surface System Testing Therapeutic Effect United States Work antimicrobial peptide bactericide bacteriocin base cathelicidin commensal microbes effective intervention enteritis fitness foodborne foodborne pathogen functional genomics gastrointestinal genome wide association study in vivo insight killings mutant natural antimicrobial novel pathogen pressure prevent public health relevance research study resistance mechanism

项目摘要

DESCRIPTION (provided by applicant): Campylobacter jejuni is the leading bacterial cause of human enteritis in the United States. Contaminated poultry meats are considered a significant source for human Campylobacter infections. Increasing resistance of C. jejuni to clinical antibiotics poses a significant threat to public health and raises an urgent need for alternative strategies to prevent and control Campylobacter infections. Antimicrobial peptides (AMPs) are short and bactericidal peptides widely present in intestine to limit bacterial infections and also increasingly recognized as a novel class of antibiotics (peptide antibiotics) to control foodborne pathogens. Notably, several potent anti-Campylobacter bacteriocins, a group of AMPs produced by commensal bacteria, dramatically reduced C. jejuni colonization in chickens and are being directed toward on-farm control of this pathogen to protect public health. As an important strategy to evade killing by potential peptide antibiotics and by host innate defense, AMP resistance mechanisms in C. jejuni are critical to understand, but are still unknown. Our preliminary studies showed that Campylobacter could develop resistance to AMPs including the bacteriocins. We have also identified a panel of genes required for AMP resistance in C. jejuni using functional genomic approaches. Based on these observations, we hypothesize that Campylobacter has evolved complex mechanisms to develop AMP resistance and counteract killing by AMPs from various sources. To test our hypothesis, we plan to i) systematically identify and characterize genetic loci involved in C. jejuni resistance to AMPs using random transposon mutagenesis and whole genome microarray; and ii) determine the direct effect of therapeutic usage of bacteriocin on the emergence and persistence of bacteriocin-resistant Campylobacter using chicken model systems. It is anticipated that the proposed studies will enable us to develop more sustainable peptide antibiotics, provide insights into the delicate interplay between Campylobacter and the host, and ultimately lead to effective intervention strategies to prevent and control Campylobacter infections in humans. PUBLIC HEALTH RELEVANCE: Campylobacter jejuni is the most prevalent foodborne bacterial pathogen causing human gastroenteritis in the U.S. The proposed research will provide novel information on the development of effective intervention strategies against C. jejuni to protect food safety and public health.

描述（由申请方提供）：空肠弯曲菌是美国人类肠炎的主要细菌病因。被污染的禽肉被认为是人类弯曲杆菌感染的重要来源。提高C.空肠弯曲菌对临床抗生素的耐药性对公众健康构成重大威胁，并迫切需要预防和控制弯曲菌感染的替代策略。抗菌肽（Antimicrobial peptides，AMP）是广泛存在于肠道中的短肽，具有杀菌作用，是一类新型的抗生素（肽类抗生素）。值得注意的是，几种有效的抗弯曲杆菌细菌素，一组由细菌产生的AMP，显着降低C。空肠在鸡中的定殖，并正致力于农场控制这种病原体以保护公众健康。AMP耐药机制是C.空肠对于理解是至关重要的，但仍然是未知的。我们的初步研究表明，弯曲杆菌可以产生耐药性的抗菌肽，包括细菌素。我们还鉴定了一组C.利用功能基因组学方法研究空肠。基于这些观察结果，我们假设弯曲杆菌已经进化出复杂的机制来发展AMP抗性并抵消来自各种来源的AMP的杀伤。为了验证我们的假设，我们计划i）系统地鉴定和表征C。使用随机转座子诱变和全基因组微阵列测定空肠对AMP的抗性;和ii）使用鸡模型系统测定细菌素的治疗性使用对细菌素抗性弯曲杆菌的出现和持续的直接影响。预计拟议的研究将使我们能够开发更可持续的肽抗生素，深入了解弯曲杆菌与宿主之间的微妙相互作用，并最终导致有效的干预策略，以预防和控制人类弯曲杆菌感染。公共卫生相关性：空肠弯曲菌是美国引起人类胃肠炎的最常见的食源性细菌病原体。空肠，以保障食品安全和公众健康。