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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（由申请人提供）：幽门螺杆菌感染是胃炎、胃溃疡和胃癌发生的主要病因。世界上大约50%的人口感染了H。pylori和H.幽门螺杆菌感染是全球主要的幽门螺杆菌健康负担。螺杆菌根除pylori联合一种以上抗生素被推荐用于感染患者，并已成为H.幽门感染虽然抗生素治疗能有效根除H。幽门螺杆菌感染后，其疗效逐渐下降。抗生素耐药是导致治疗失败的主要原因，已成为H.幽门感染因此，迫切需要开发能够根除H.但不易产生耐药性。合成抗菌寡肽（AMP）是近年来出现的一种新型抗菌药物，可用于对抗多重耐药微生物。然而，这些肽对H. pylori很少被检测。这项提议的总体目标是设计一种新的多肽，可以选择性地杀死H。pylori感染，探讨其在根除H.幽门螺杆菌感染及其相关的胃疾病。在具体目标1中，我们将确定具有独特螺旋结构的多肽的抗微生物活性。我们将设计和开发在酸性pH下可以从非螺旋结构转化为螺旋结构的多肽，以选择性地杀死H。幽门。在具体目标2中，我们将探索这些pH激活多肽在根除H. pylori感染和H.幽门引起的胃病我们还将确定这些肽对耐药的H. pylori菌株。这些体外、细胞基础和体内动物实验将为开发多肽作为根除H. pylori感染，并为根除H. pylori感染及预防H.幽门介导的胃疾病。