Electroceutical disinfection strategies impair the motility of pathogenicPseudomonas aeruginosaandEscherichia coli

Abstract

Electrotaxis or galvanotaxis refers to the migration pattern of cells induced in response to electrical potential. Although it has been extensively studied in mammalian cells, electrotaxis has not been explored in detail in bacterial cells; information regarding the impact of current on pathogenic bacteria is severely lacking. Therefore, we designed a series of single and multi-cue experiments to assess the impact of varying currents on bacterial motility dynamics in pathogenic multi-drug resistant (MDR) strains of Pseudomonas aeruginosa and Escherichia coli using a microfluidic platform. Motility plays key roles in bacterial migration and the colonization of surfaces during the formation of biofilms, which are inherently recalcitrant to removal and resistant to traditional disinfection strategies (e.g. antibiotics). Use of the microfluidic platform allows for exposure to current, which can be supplied at a range that is biocidal to bacteria, yet physiologically safe in humans (single cue). This system also allows for multi-cue experiments where acetic acid, a relatively safe compound with anti-fouling/antimicrobial properties, can be combined with current to enhance disinfection. These strategies may offer substantial therapeutic benefits, specifically for the treatment of biofilm infections, such as those found in the wound environment. Furthermore, microfluidic systems have been successfully used to model the unique microfluidic dynamics present in the wound environment, suggesting that these investigations could be extended to more complex biological systems. Our results showed that the application of current in combination with acetic acid has profound inhibitory effects on MDR strains of P. aeruginosa and E. coli, even with brief applications. Specifically, E. coli motility dynamics and cell survival were significantly impaired starting at a concentration of 125 μA DC and 0.31% acetic acid, while P. aeruginosa was impaired at 70 μA and 0.31% acetic acid. As these strains are relevant wound pathogens, it is likely that this strategy would be effective against similar strains in vivo and could represent a new approach to hasten wound healing.

Oleate Epoxides Derived from Palm Oil as New Anticancer Agents: Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies Against FASN Protein

“…Cerulenin and orlistat have been reported to have strong anticancer activity through the inhibition of FASN protein in multicell cancer targets. [26,29,30,53] Molecular docking of epoxidized oleate to the thioesterase subunit of FASN has been conducted through validation with redocking to set the grid box. Redocking of orlistat as a native ligand of FASN protein (2PX6) gives an RMSD value of 1.39 Å and a binding affinity value of À 8.6 kcal/mol.…”

“…[27,28] The anticancer effects of cerulenin have been demonstrated by inhibiting the fatty acid synthase protein (FASN) in cancer cells. [26,29] By the same mechanism, the commercial drug orlistat used to treat obesity also has anticancer effects by inhibiting the FASN protein. [30] FASN is strongly related to the survival capability of cancer cells.…”

“…Monoepoxide compounds such as cerulenin can inhibit fatty acid and steroid biosynthesis pathways in the anticancer activity assay against multicellular cancer targets. [26] The presence of an oxirane ring in cerulenin yielded attractive properties due to their potent interactions with some intracellular proteins. Generally, epoxide derivatives could react with nucleophilic groups (such as amino, sulfur, and oxygen functional groups) on biomolecules such as proteins and DNA, causing cytotoxicity in cancer cells.…”