Meldrum acid derivatives may be inhibitors of the MepA efflux pump

Meldrum acid derivatives may be inhibitors of the MepA efflux pump

• Author
• Isaac Moura Araújo
• Co-authors
• Luís Pereira de Morais , Raimundo Luiz Silva Pereira , Cícera Datiane de Morais Oliveira-Tintino , Saulo Relison Tintino , Sheila Alves Gonçalves , Ana Carolina Justino de Araújo , Henrique Douglas Melo Coutinho
• Abstract

•  

   

   

  Introduction:The indiscriminate use of antibiotics has led to a concerning increase in bacterial strains resistant to these drugs. Efflux pumps, which are proteins capable of expelling antibiotics from bacterial cells, have emerged as a major mechanism of bacterial resistance. In the ongoing pursuit to overcome and reduce bacterial resistance, novel substances are being explored as potential efflux pump inhibitors. Meldrum's acid, a synthetic molecule widely studied for its role in synthesizing bioactive compounds, holds promise in this regard. Aims: Therefore, the objective of this study is to evaluate the antibacterial activity of three derivatives of meldrum's acid and assess their ability to inhibit efflux mechanisms, employing in vitro approaches. Methods: The antibacterial activity of the derivatives was assessed using a broth microdilution testing method with K2068 strain, wich expresses the MepA eflux pump and the fluorimetry assay was performed by visualizing the fluorescence intensity of ethidium bromide (EtBr) on a UV transilluminator. Results: the derivatives did not exhibit direct antibacterial activity on their own. However, they displayed a significant effect in enhancing the efficacy of antibiotics, suggesting a potential role in potentiating their effects. Furthermore, fluorescence emission assays using ethidium bromide indicated that the derivatives could potentially block efflux pumps, as they exhibited fluorescence levels comparable to the positive control. These findings highlight the potential of meldrum's acid derivatives as effective inhibitors of efflux pumps. By targeting these mechanisms, the derivatives offer a promising avenue to enhance the effectiveness of antibiotics and combat bacterial resistance. This study underscores the importance of exploring novel strategies in the fight against bacterial resistance and provides valuable insights into the potential of meldrum's acid derivatives as efflux pump inhibitors. Further research and exploration in this field are warranted to fully exploit their therapeutic potential.

• Keywords
• Antibacterial, Eflux pump, Fluorimetry.
• Modality
• Pôster
• Subject Area
• Biology, Pharmacology and Physiology