Supramolecular self-associating amphiphiles (SSAs) as enhancers of antimicrobial agents towards Escherichia coli (E. coli)

Abstract

Using supramolecular self-associating amphiphiles (SSAs) and antimicrobial/therapeutic agents as combination therapies that lead to increased efficacy against Escherichia coli.

Cooperative cation co-transport by supramolecular self-associating amphiphiles

“…4,26,27 Supramolecular, self-associating amphiphiles (SSAs) are a class of small molecule, amphiphilic salts developed by the Hiscock group that have been shown to act as antimicrobial agents 28 and efficacy enhancers for both anticancer and antimicrobial agents. [29][30][31][32] Recent studies have established that many SSAs, including the intrinsically fluorescent, benzothiazole substituted 1 and 2 (Figure 1), display aggregation-dependent antimicrobial activity against both Gram-positive MRSA USA300 and Gram-negative bacteria Escherichia coli (E. coli) DH10beta. 28,33 In particular, SSA 2 has been observed to coat and penetrate both bacterial cell and cancer cell membranes in fluorescence microscopy experiments.…”

The phospholipid membrane compositions of bacterial cells, cancer cell lines and biological samples from cancer patients

“…39 Finally, within the scope of our own work, we have shown that a novel class of supramolecular self-associating amphiphiles (SSAs) can coordinate to and permeate both bacterial 40 and cancer cell membranes, 41 causing SSAs to be identied as anticancer agents, 41 antimicrobials 40,42,43 and efficacy enhancers for known therapeutic agents. 41,44 The analysis herein seeks to aid the effort to understand and characterise interactions between therapeutic candidates and phospholipid membranes by creating a resource detailing the phospholipid membrane composition of cancer and bacterial cells.…”

Di-anionic self-associating supramolecular amphiphiles (SSAs) as antimicrobial agents against MRSA andEscherichia coli

“…22 Our work in this field to date has led to the identification of a novel class of supramolecular self-associating amphiphiles (SSAs) 23,24 as: selective phospholipid membrane co-ordination agents, 25,26 antimicrobial agents against Gram-negative Escherichia coli (E. coli) and Gram-positive MRSA, [27][28][29] anticancer agents, 30 potential drug delivery vehicles, 31 and therapeutic efficacy enhancement agents. 30,32 Here, we present a series of three next-generation di-anionic SSAs (1, 3, 4 -Fig. 1), and report the self-associative properties of these amphiphilic salts in the solid state and in aqueous solutions, before exploring the potential of these compounds as antimicrobial agents against both E. coli and clinically relevant MRSA.…”

“…We have previously shown mono-anionic SSAs to interact with, and permeate bacterial membranes. 25,28,30,32 The results summarised in Table 2 show the di-anionic SSAs have an enhanced antimicrobial selectivity for Gram +ve MRSA over Gram Àve E. coli and a low cytotoxicity profile against human red blood cells. Interestingly, when ranking the % haemolysis induced by 1, 3-5, this was found to differ from the ranking of antimicrobial activity.…”

“…The antimicrobial efficacy of di-anionic SSAs 1, 3 and 4 was found to decrease with increasing % of the SSAs anionic component to be incorporated into solid-like aggregated structures (Table 1 -quantitative 1 H NMR). This causes us to hypothesise that the di-anionic SSA mode of action maybe dependent on a critical concentration of SSA to arrive at the microbial surface in an aggregated form before an antimicrobial effect can be achieved, 24,27,28,32 in an analogous fashion to that described by the antimicrobial carpet mechanism. 34 However, it is also conceivable that the flexibility and lipophobicity of the di-anion central linker may be a contributing factor to aid membrane permeation, through effective shielding of the SSA anions charged functionalities.…”