Antimicrobial activity of pH-activated polypeptides toward H. pylori

pH 激活多肽对幽门螺杆菌的抗菌活性

基本信息

批准号：
8873154
负责人：
Lin-Feng Chen
金额：
$ 19.83万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-05-01 至 2017-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8873154
关键词：
Adopted Affect Amoxicillin Animal Experiments Antibiotic Resistance Antibiotic Therapy Antibiotics Bacteria Benign Biological Models Cells Charge Clarithromycin Cultured Cells Cytoplasm Data Development Disease Drug resistance Electrostatics Engineering Gastric ulcer Gastritis Gerbils Glutamic Acid Goals Health Helicobacter Infections Helicobacter pylori Imidazole In Vitro Infection prevention Malignant - descriptor Mediating Membrane Microbe Molecular Conformation Multi-Drug Resistance Oligonucleotides Patients Penetration Peptides Physiological Population Proton Pump Inhibitors Public Health Resistance Side Specificity Stomach Carcinoma Stomach Diseases Structure Surface Testing Therapeutic Toxic effect Treatment Failure Vertebral column antimicrobial antimicrobial drug antimicrobial peptide bactericide base carboxyl radical combat commensal microbes compliance behavior cytotoxicity design effective therapy in vivo insight killings membrane activity microbial novel pathogen polypeptide public health relevance

项目摘要

DESCRIPTION (provided by applicant): Helicobacter pylori infection is the major etiological factor in the development of gastritis, gastric ulcers, and gastric carcinoma. About 50% of the world's population is infected with H. pylori and H. pylori infection presents a major global publi health burden. Eradication of H. pylori with more than one antibiotic is recommended for infected patients and has become the first line treatment for H. pylori infection. While antibiotic therapy is effective in eradicating H. pylori infection, its efficacy is gradually decreasing. Antibiotic resistance is the major cause of treatment failure and has become the most evident challenge to treatment of H. pylori infection. It is urgently required to develop novel therapies that are able to eradicate H. pylori but not easily susceptible to resistance. Synthetic antimicrobial oligo peptides (AMP) have recently emerged as novel antimicrobial agents in combating multidrug resistant microbes. However, the microbiocidal activity of these peptides on H. pylori has rarely been tested. The overall goal of this proposal is to design a new class of polypeptides that would selectively kill H. pylori under acidic conditions and explore their therapeutic potentials in eradication of H. pylori infection and its associated gastric diseases. n Specific Aim 1, we will determine the anti-microbial activity of polypeptides with unique helical structure. We will design and develop polypeptides that can be converted from a non-helical structure to a helical structure under acidic pH to selectively kill H. pylori. In Specific Aim 2, e will explore the anti-microbial potential of these pH-activated polypeptides in eradication of H. pylori infection and H. pylori-induced gastric diseases. We will also determine the bactericidal activity of these peptides toward antibiotic-resistant H. pylori strains. These in vitro, cell-base, and in vivo animal experiments will provide new insights into the development of polypeptides as effective agents for eradication of H. pylori infection and also provide new information on nontraditional therapy for the eradication of H. pylori infection and the prevention H. pylori- mediated gastric diseases.

描述（由应用提供）：幽门螺杆菌感染是胃炎，胃溃疡和胃癌的发展的主要病因。全世界约有50％的人口感染了幽门螺杆菌和幽门螺杆菌感染，这是全球主要的公共卫生伯恩。建议对受感染的患者消除幽门螺杆菌用多种抗生素，并已成为幽门螺杆菌感染的第一线治疗。而抗生素治疗有效地消除，其有效性正在逐渐降低。抗生素耐药性是治疗失败的主要原因，已成为对幽门螺杆菌感染治疗的最大证据挑战。迫切需要开发能够降生幽门螺杆菌但不容易受到抗性的新型疗法。合成抗菌寡辣椒（AMP）最近在打击多药耐药微生物方面已成为新型抗菌剂。然而，这些肽对幽门螺杆菌的微生物活性很少被测试。该提案的总体目标是设计一类新的多肽，这些多肽可以在酸性条件下有选择地杀死幽门螺杆菌，并探索其在根除幽门螺杆菌感染及其相关胃疾病时的治疗潜力。 n特定的目标1，我们将确定具有独特的螺旋结构的多肽的抗微生物活性。我们将设计和开发可从非螺旋结构转换为酸性pH下的螺旋结构以选择性地杀死幽门螺杆菌的多肽。在特定的目标2中，E将探索这些pH激活多肽在洗脱幽门螺杆菌感染和幽门螺杆菌诱导的胃病中的抗菌潜力。我们还将确定这些肽对抗生素抗生素的幽门螺杆菌菌株的细菌活性。这些体外，细胞碱和体内动物实验将为多肽的发展提供新的见解，作为幽门螺杆菌感染辐射的有效药物，并为消除幽门螺杆菌感染的非传统治疗提供新的信息，以消除幽门螺杆菌感染和预防H. Pylori介导的胃胃疾病。