Investigation of efflux pump biocide and antibacterial resistance mitigation in organisms within biofilms

外排泵杀菌剂和生物膜内生物体抗菌耐药性缓解的研究

• 批准号: BB/P000134/1
• 负责人: Paul Humphreys
• 金额: $ 5.12万
• 依托单位: University of Huddersfield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2016
• 资助国家: 英国
• 起止时间: 2016 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FP000134%2F1
• 关键词: Investigation; efflux; pump; biocide; antibacterial

Chlorhexidine (CHG) and other bis biguanides are important agents in clinical settings for the disinfection of skin sites, catheters and other medical implants. In all these cases the formation of biofilms is associated with negative clinical outcomes in part due to the protection that biofilms provide against the antimicrobial agents employed. In recent years the challenge presented by biofilms has been exacerbated by the emergence of a reduced susceptibility to CHG amongst pathogens such as Pseudomonas sp and MRSA. this reduced susceptibility is mediated by increased efflux pump activity which prevents the required CHG concentration from accumulation within the bacterial cell. A number of effective efflux pump inhibitors (EPI) exist but these compounds have not been compatible with existing chlorhexidine formulations. In preliminary studies one group of EPIs (cationic dendritic polymers) were successfully integrated into chlorhexidine formulations and showed promise in preliminary investigations. This project will expand on this preliminary data by investigating the impact of a range of formulations against biofilms of clinically relevant isolates in order to develop a new range of anti biofilm chlorhexidine/EPI formulations.

氯己定（CHG）和其他双胍类化合物是临床环境中用于皮肤部位、导管和其他医疗植入物消毒的重要试剂。在所有这些情况下，生物膜的形成与负面的临床结果相关，部分原因是生物膜提供了针对所用抗菌剂的保护。近年来，生物膜所带来的挑战因病原体如假单胞菌和MRSA对CHG的敏感性降低而加剧。这种降低的敏感性是由增加的外排泵活性介导的，该外排泵活性防止所需的CHG浓度在细菌细胞内积累。存在许多有效的外排泵抑制剂（EPI），但这些化合物与现有的氯己定制剂不相容。在初步研究中，一组EPI（阳离子树枝状聚合物）被成功地整合到洗必泰制剂中，并在初步研究中显示出希望。该项目将通过研究一系列制剂对临床相关分离株生物膜的影响来扩展该初步数据，以开发一系列新的抗生物膜洗必泰/EPI制剂。