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Incorporation of a biofilm dispersion autoinducer into an antimicrobial ointment for the treatment of topical wounds

将生物膜分散自诱导剂掺入抗菌软膏中用于治疗局部伤口

基本信息

批准号：
9902641
负责人：
Paul Woods
金额：
$ 5.5万
依托单位：
EXCELSIOR BIOFILMS, LLC
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-20 至 2019-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9902641
关键词：
Acinetobacter baumannii Adhesions Animal Model Antibiotics Bacitracin Bacteria Bacteriophages Candida albicans Caring Cell Communication Cells Chronic Disease Combined Modality Therapy Communication Computer software Decenoic Acid Development Drug resistance Enzymes Exposure to Formulation Funding Goals Gram-Negative Bacteria Gram-Positive Bacteria Growth Histologic Human Image Infection Investigation Laboratories Lasers Measures Metabolic Methods Microbial Biofilms Modeling Monitor Mus National Institute of Allergy and Infectious Disease Neomycin Nutrient Ointments Petrolatum Phase Physiological Physiology Polymyxin B Population Preparation Prevention Prevention strategy Pseudomonas aeruginosa Research Safety Scanning Signal Transduction Signaling Molecule Skin Slide Staphylococcus aureus Sterile coverings Structure System Testing Therapeutic Topical Antibiotic Topical application Translational Research United States National Institutes of Health Work Wound Healing antimicrobial antimicrobial drug base cell motility cytotoxicity expectation experimental study fungus improved in vitro Model inhibitor/antagonist innovation keratinocyte microbial monolayer nanomolar novel pathogen pressure prevent priority pathogen quorum sensing response treatment effect treatment strategy uptake wound wound closure

项目摘要

Project Summary Three species of biofilm-forming bacteria, Acinetobacter baumannii, Pseudomonas aeruginosa and Staphylococcus aureus, were recently identified by WHO as critical or high priority pathogens for which new antibiotics or antimicrobial treatments are urgently needed1. We believe the inability to effectively prevent or treat a wide range of biofilm-related chronic diseases may be overcome by using a biofilm dispersal signal as an adjunctive to conventional antimicrobial therapies. Studies in our laboratory have demonstrated that P. aeruginosa produces a quorum sensing molecule, cis-2-decenoic acid (cis-DA), that is responsible for auto- induction of the native dispersion response in biofilm bacteria. This signaling molecule has been shown to induce a physiological change in bacteria, causing them to disaggregate from a biofilm and alter their physiology, rendering them more susceptible to antibiotics. Additionally, cis-DA has been shown to induce biofilm dispersion in a wide range of Gram-negative and Gram-positive bacteria, as well as fungi. Here we propose to determine the degree to which cis-DA can improve the anti-biofilm activity of a petroleum jelly-based ointment with embedded antimicrobials (polymyxin B, bacitracin and neomycin). Experiments will examine the killing of pre- formed single- and multi-species biofilms. After confirming that the cis-DA adjunctive treatment is not toxic to human keratinocytes, we will test the effects on in vitro models of wounded and infected skin. In the final line of investigation, we will examine the efficacy and safety of the treatment in murine wound model. We anticipate that this work will result in an antimicrobial/anti-biofilm formulation that will improve current treatment and prevention strategies against biofilm infections in topical wounds.

项目总结