Bacterial food-borne and nosocomial infections are a public health issue around the world that is exacerbated by biofilm formation and acquired resistance to antibiotics. New therapies focusing on the prevention of biofilm formation may help to face these challenges. In this study, the antibiofilm activity of Cu2+ and Fe3+ complexes formed with an EDTA-based phenylene macrocycle and its acyclic analogue (edtaod and edtabz) was evaluated against Escherichia coli O157: H7, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella enterica sub. enterica serovar Typhimurium and Staphylococcus aureus. In general, edtabz ligand and complexes, at 0.25–1 mM, presented higher biomass reduction of biofilms than edtaod and its complexes against L. monocytogenes (edtabz and Fe-edtabz; 66.1–99.1% and 78.3–97.4%, respectively), P. aeruginosa (edtabz; 66.4–88.1%), S. aureus (Cu-edtabz; 27.4–73.9%) and Salmonella Typhimurium (Cu-edtabz; 19.4–75.5%). While biofilm formation of E. coli was inhibited by Cu-edtaod with a biomass reduction of 71.5–80.7%. Additionally, antibiofilm activity of edtaod was enhanced by Cu2+ or Fe3+ complexation. Correlation analysis showed that molecular properties such as molecular weight, volume and the number or rotatable bonds have a positive relationship with antibiofilm activity of compounds. Principal component analysis showed that biofilm inhibition patterns of Salmonella Typhimurium, L. monocytogenes and P. aeruginosa were similar and closely related with molecular volume of EDTA complexes. Overall, the results suggest that EDTA-based phenylene macrocycles and its Cu2+ and Fe3+ complexes with its antibiofilm activity can be useful to prevent biofilm related infections.
Bibliographical noteFunding Information:
Authors acknowledge support from Consejo Nacional de Ciencia y Tecnología (CONACYT, Mexico), for a graduate doctoral scholarship (2019-000037-02NACF-25834). Also, we thank the Secretaría de Educación Pública, México (SEP) for postdoctoral scholarship grant PRODEP 511-6/2019-15776.
© 2021 Elsevier Ltd
- Anti-virulence therapy
- Biofilm prevention
- Coordination chemistry
- Pathogenic bacteria