Antibacterial effects of quaternary bis-phosphonium and ammonium salts of pyridoxine on Staphylococcus aureus cells: A single base hitting two distinct targets?

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 Ca(2+) ions the MIC and MBC values of ammonium salt increased 100-fold, suggesting that Ca(2+) ions can successfully impede the membrane Ca(2+) 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.

Fluconazole-Pyridoxine Bis-Triazolium Compounds with Potent Activity against Pathogenic Bacteria and Fungi Including Their Biofilm-Embedded Forms

“…Therefore, it can be suggested that the cell wall damage associated with the removal of Ca 2+ ions is one of the possible mechanisms of their antibacterial activity. Similar observations have been reported in our recent paper [53] for a series of quaternary bis-phosphonium salts of pyridine derivatives, which exhibited broad-spectrum antibacterial activity against Grampositive pathogens including methicillin-resistant strains of S. aureus.…”

A Novel Triphenylphosphonium Carrier to Target Mitochondria without Uncoupling Oxidative Phosphorylation

“…33 Synthesis of TPP + -TAMRA conjugates (42 and 43) is shown in Figure 6A. Potassium phthalimide (35) was stirred with excess 1,10-dibromodecane (34) to give 10-bromodecylphthalimide (36). Column chromatography was used to remove the unreacted dibromoalkane.…”

Nanotechnology as a Novel Approach in Combating Microbes Providing an Alternative to Antibiotics

“… Several toxic pathways. [ 331 ] [ 332 ] Composite-Based Nanomaterials Ceramic Matrix Nano-composites 1–100 S. aureus E. coli High antimicrobial effect Inhibit the bacterial growth Physical interaction Particle size Heat pressure [ 333 ] Metal Matrix Nano-composites 1–100 A. baumannii S. aureus E. coli K. pneumonia Inhibit the bacterial growth Physical interaction formation of irregular pores in the outer membrane of bacteria Particle size Depends on the content in the medium [ 334 ] Polymer Matrix Nano-composites 1–100 A. baumannii S. aureus E. coli K. pneumonia MDR Inhibit the bacterial growth Physical interaction Depends on the content in the medium [ 335 ] …”