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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.