Novel antimony-based antimicrobial drug targets membranes of Gram-positive and Gram-negative bacterial pathogens
Abstract
Antimicrobial resistance (AMR) poses a significant worldwide public health crisis that continues to threaten our ability to successfully treat bacterial infections. With the decline in effectiveness of conventional antimicrobial therapies and the lack of new antibiotic pipelines, there is a renewed interest in exploring the potential of metal-based antimicrobial compounds. Antimony-based compounds with a long history of use in medicine have re-emerged as potential antimicrobial agents. We previously synthesized a series of novel organoantimony(V) compounds complexed with cyanoximates with a strong potential of antimicrobial activity against several AMR bacterial and fungal pathogens. Here, five selected compounds were studied for their antibacterial efficacy against three important bacterial pathogens: Pseudomonas aeruginosa, Escherichia coli, and Staphylococcus aureus. Among five tested compounds, SbPh4ACO showed antimicrobial activity against all three bacterial strains with the MIC of 50–100 µg/mL. The minimum bactericidal concentration/MIC values were less than or equal to 4 indicating that the effects of SbPh4ACO are bactericidal. Moreover, ultra-thin electron microscopy revealed that SbPh4ACO treatment caused membrane disruption in all three strains, which was further validated by increased membrane permeability. We also showed that SbPh4ACO acted synergistically with the antibiotics, polymyxin B and cefoxitin used to treat AMR strains of P. aeruginosa and S. aureus, respectively, and that at synergistic MIC concentration 12.5 µg/mL, its cytotoxicity against the cell lines, Hela, McCoy, and A549 dropped below the threshold. Overall, the results highlight the antimicrobial potential of novel antimony-based compound, SbPh4ACO, and its use as a potentiator of other antibiotics against both Gram-positive and Gram-negative bacterial pathogens.
Department(s)
Chemistry and Biochemistry
Document Type
Article
DOI
10.1128/spectrum.04234-23
Keywords
broad spectrum, combination therapy, cytotoxicity
Publication Date
6-1-2024
Recommended Citation
Pinks, Kevin E.; Gerasimchuk, Nikolay N.; Salpadoru, Tarosha; Lieberman, Jacob A.; Cotton, Kaitlyn; Wozniak, Karen L.; and Patrauchan, Marianna A., "Novel antimony-based antimicrobial drug targets membranes of Gram-positive and Gram-negative bacterial pathogens" (2024). Faculty Scholarship. 360.
https://bearworks.missouristate.edu/articles00/360
Journal Title
Microbiology Spectrum
