Resensitizing multidrug resistant bacteria to antibiotics by targeting bacterial response regulators.
Year: 2018
Type: other
Abstract: Many of the currently available antibiotics target a narrow spectrum of metabolic processes required for cellular growth. The rate at which bacteria are developing resistance leads to traditional approaches no longer offering long-term protection. Bacteria often avoid antibiotics through the use of biofilms. Biofilms act as a protective barrier against harsh environments and leave bacteria resistant to antibiotic treatments. As such, understanding how biofilms are formed and developing small molecule therapies are vital steps in combating antibiotic resistance. Formation of biofilms is controlled in part by transcription factors known as response regulators. Response regulators are part of two-component systems which allow the cell to detect and respond to changes in its environment and are used to trigger quorum sensing and virulence factors. Response regulators have been highly sought after as drug targets. Knocking out function with drug therapies would likely inhibit pathogenic behavior, making response regulators a potent new approach that has not yet been exploited. The dynamic nature of response regulators makes structure based drug design challenging. Fortunately, a class of 2-aminoimidazole (2-AI) compounds can bind bacterial response regulators, inhibiting biofilm formation and resensitize multidrug resistant bacteria to antibiotics. This work highlights the interactions between 2-AIs and the biofilm response regulators BfmR from Acinetobacter baumannii and QseB from Francisella tularensis . These studies have led to a model for response regulator inhibition by 2-AIs. Understanding the impact of 2AIs on response regulators and their mechanism of interaction will lead to the development of more potent compounds that will serve as adjuvant therapies with broad-range antibiotics.
Institution: RTI International
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W2919078388