Abstract
We studied the effects of quaternary bis-phosphonium and bis-ammonium salts of pyridoxine with lipophilic substituents on the survival and morphology of Staphylococcus aureus cells. We found that, while originating from the same base, they exhibit considerably different antimicrobial mechanisms. In the presence of Ca2+ ions the MIC and MBC values of ammonium salt increased 100-fold, suggesting that Ca2+ ions can successfully impede the membrane Ca2+ ions exchange required for ammonium salt incorporation. In contrast, in the presence of quaternary phosphonium salt, the artificial capsular-like material was formed around the cells and the filamentous and chain-like growth of the cells was observed suggesting the disruption of the cell division mechanisms. Altogether, both pyridoxine derivatives successfully inhibited the growth of gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Bacillus subtilis) and Escherichia coli considerably, while demonstrated nearly no effect against Klebsiella pneumoniae and Pseudomonas aeruginosa. We suggest that due to their effects on distinct and likely complementary targets the derivatives of pyridoxine represent potentially perspective antibacterials with complicated adaptation and thus with lower risk of drug resistance development.
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Acknowledgments
This work was funded by the subsidy allocated to Kazan Federal University by Federal Targeted Program for Research and Development in Priority Areas of Development of the Russian Scientific and Technological Complex for 2014–2020 (Project No. 14.575.21.0037 from 27.06.2014, the unique identifier of the agreement RFMEF157514X0037).
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Nikitina, E.V., Zeldi, M.I., Pugachev, M.V. et al. Antibacterial effects of quaternary bis-phosphonium and ammonium salts of pyridoxine on Staphylococcus aureus cells: A single base hitting two distinct targets?. World J Microbiol Biotechnol 32, 5 (2016). https://doi.org/10.1007/s11274-015-1969-0
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DOI: https://doi.org/10.1007/s11274-015-1969-0