Investigating the Modes of Action of the Antimicrobial Chalcones BC1 and T9A

Abstract

Xanthomonas citri subsp. citri (X. citri) is an important phytopathogen and causes Asiatic Citrus Canker (ACC). To control ACC, copper sprays are commonly used. As copper is an environmentally damaging heavy metal, new antimicrobials are needed to combat citrus canker. Here, we explored the antimicrobial activity of chalcones, specifically the methoxychalcone BC1 and the hydroxychalcone T9A, against X. citri and the model organism Bacillus subtilis. BC1 and T9A prevented growth of X. citri and B. subtilis in concentrations varying from 20 µg/mL to 40 µg/mL. BC1 and T9A decreased incorporation of radiolabeled precursors of DNA, RNA, protein, and peptidoglycan in X. citri and B. subtilis. Both compounds mildly affected respiratory activity in X. citri, but T9A strongly decreased respiratory activity in B. subtilis. In line with that finding, intracellular ATP decreased strongly in B. subtilis upon T9A treatment, whereas BC1 increased intracellular ATP. In X. citri, both compounds resulted in a decrease in intracellular ATP. Cell division seems not to be affected in X. citri, and, although in B. subtilis the formation of FtsZ-rings is affected, a FtsZ GTPase activity assay suggests that this is an indirect effect. The chalcones studied here represent a sustainable alternative to copper for the control of ACC, and further studies are ongoing to elucidate their precise modes of action.

Chalcones: Synthetic Chemistry Follows Where Nature Leads

“…In silico studies established DNA binding and molecular docking of these compounds. There are several other examples of synthesis antibacterial chalcones and assessment of their modes of action available in the literature [93][94][95][96][97]…”

Selectivity and Activity of Benzene‐1,2,4‐triol and its Dimers as Antimicrobial Compounds Against Xanthomonas citri subsp. citri

“…Other mechanisms of antibacterial action include disruption of cell wall synthesis or cell division [4b,d–f] – either at the centromere or the septum ‐, reduction in respiratory cell activity and reduction in the level of intracellular ATP, [4c] generation of reactive oxygen species (ROS) and iron sequestration (e. g. siderophores).…”

Photophysical Study and Biological Applications of Synthetic Chalcone-Based Fluorescent Dyes

“…For S. aureus 1466, the MIC values of 3a – f ranged from 250 to 375 μM, which is similar to that for E. coli 780 ( Table 3 ), whereas the MBC values were much higher (1000 μM). The greater antibacterial activities of chalcones against E. coli 780 than S. aureus 1466 might be due to the thinness of the peptidoglycan layer in Gram-negative bacteria [ 28 , 46 , 47 , 48 ]. According to the MIC and MBC values, 3d showed the best antimicrobial activities against E. coli 780 and S. aureus 1466 compared to the other compounds among the series.…”

“…Some chalcone-based fluorescent compounds have been evaluated to have good photophysical properties [ 26 , 27 , 28 , 29 ], and some showed promising results in biological applications. For example, the diamino-chalcone library was discovered to comprise fluorescent probes for mouse embryonic stem cells, targeting glycoproteins on stem cell surface [ 13 ].…”