Omneya Helmy

Citation:

Ibrahim, K. A., M. O. N. A. T. KASHEF, T. R. Elkhamissy, M. A. Ramadan, and O. M. N. E. Y. A. M. HELMY, "Aspartate α-decarboxylase a new therapeutic target in the fight against infection.", Frontiers in microbiology, vol. 13, pp. 1019666, 2022.

Abstract:

Effective eradication therapy for is a worldwide demand. Aspartate α-decarboxylase (ADC) was reported as a drug target in . , in an study, with malonic acid (MA) as its inhibitor. We evaluated eradicating . infection through ADC inhibition and the possibility of resistance development. MA binding to ADC was modeled molecular docking. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of MA were determined against . ATCC 43504, and a clinical . isolate. To confirm selective ADC inhibition, we redetermined the MIC in the presence of products of the inhibited enzymatic pathway: β-alanine and pantothenate. HPLC was used to assay the enzymatic activity of . 6x-his tagged ADC in the presence of different MA concentrations. . strains were serially exposed to MA for 14 passages, and the MICs were determined. Cytotoxicity in different cell lines was tested. The efficiency of ADC inhibition in treating . infections was evaluated using a Sprague-Dawley (SD) rat infection model. MA spectrum of activity was determined in different pathogens. MA binds to . ADC active site with a good docking score. The MIC of MA against . ranged from 0.5 to 0.75 mg/mL with MBC of 1.5 mg/mL. Increasing β-alanine and pantothenate concentrations proportionally increased MA MIC. The 6x-his tagged ADC activity decreased by increasing MA concentration. No resistance to ADC inhibition was recorded after 14 passages; MA lacked cytotoxicity in all tested cell lines. ADC inhibition effectively eradicated . infection in SD rats. MA had MIC between 0.625 to 1.25 mg/mL against the tested bacterial pathogens. In conclusion, ADC is a promising target for effectively eradicating . infection that is not affected by resistance development, besides being of broad-spectrum presence in different pathogens. MA provides a lead molecule for the development of an anti-helicobacter ADC inhibitor. This provides hope for saving the lives of those at high risk of infection with the carcinogenic . .