期刊
DRUG AND CHEMICAL TOXICOLOGY
卷 35, 期 3, 页码 310-315出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/01480545.2011.614620
关键词
2-aminoimidazole; adjuvant; biofilm; Caenorhabditis elegans; toxicity; Toxicity of 2-aminoimidazole; antibiofilm agents
资金
- National Institutes of Health [GM55769]
- North Carolina Biotechnology Center
- National Science Foundation [IOS-0617897, IOS-1021144]
- V Foundation for Cancer Research
- Division Of Integrative Organismal Systems
- Direct For Biological Sciences [1314144, 1021144] Funding Source: National Science Foundation
Biofilm formation is a ubiquitous bacterial defense mechanism and has been shown to be a primary element in the antibiotic resistance of many human diseases, especially in the case of nosocomial infections. Recently, we have developed several compound libraries that are extremely effective at both dispersing preexisting biofilms and also inhibiting their initial formation. In addition to their antibiofilm properties, some of these molecules are able to resensitize resistant bacterial strains to previously ineffective antibiotics and are being assessed as adjuvants. In this study, we evaluated the toxic effects of three of our most effective 2-aminoimidazole compounds (dihydrosventrin, RA, and SPAR) using a rapid pipeline that combines a series of assays. A methylthiazolyldiphenyl-tetrazolium assay, using the HaCaT keratinocyte cell line was used to determine epidermal irritants and was combined with Caenorhabditis elegans fecundity assays that demonstrated the effects of environmental exposure to various concentrations of these molecules. In each case, the assays showed that the compounds did not exhibit toxicity until they reached well above their current biofilm dispersion/inhibition concentrations. The most effective antibiofilm compound also had significant effects when used in conjunction with several standard antibiotics against resistant bacteria. Consequently, it was further investigated using the C. elegans assay in combination with different antibiotics and was found to maintain the same low level of toxicity as when acting alone, bolstering its candidacy for further testing as an adjuvant.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据