“Leaching or not leaching”: an alternative approach to antimicrobial materials via copolymers containing crown ethers as active groups

Abstract

In this work, new copolymers containing either MMA and 18C6 crown-ether pendants, or PEG, MMA and 18C6 crown-ether pendants were synthesized to test the idea that sequestering structural alkali-earth ions from the bacterial outer membrane (OM) may lead to bacterial death. The copolymers were obtained either via uncontrolled radical polymerization or ATRP; the latter approached allowed us to produce not only linear copolymers but also branched Y-like structures. After checking for the capability of complexing magnesium and calcium ions, the antimicrobial activity of all copolymers was tested placing their casted plaques in contact with pure water E. coli suspensions. All plaques adsorbed alkali-earth ions and killed bacteria, albeit with different antimicrobial efficiencies. Differences in the latter characteristic were attributed to different plaque roughness. The role of the 18C6 crown-ether pendants was elucidated by pre-saturating plaques with Mg/Ca ions, the marked reduction in antimicrobial efficiency indicating that losing the latter from OM due to surface complexation does play an important role in killing bacteria at short (<5 h) contact times. At longer times, the mode of action is instead related to the poly-cationic nature acquired by the plaques due to ion sequestering.

Escherichia coli as a Model for the Description of the Antimicrobial Mechanism of a Cationic Polymer Surface: Cellular Target and Bacterial Contrast Response

“…It also emerged that during the T phase, the film induces an increased expression of pld A, pag P, waa A, and waa C genes, indicating that OM undergoes serious structural damages and confirming the results on the altered permeability. A major expression of pld A and pag A genes indicates an increase of the amount of phospholipids in the outer leaflet and an imbalance in the concentrations of divalent ions that stabilize LPS. − The latter result is in accordance with previous data reporting the bactericidal activity of surfaces made of polymer containing crown ethers pendants as chelating agents of divalent cations . The cation imbalance also induced a loss of LPS. , This last hypothesis is supported by the increase in the expression of the biosynthetic genes of the LPS core, waa A and waa C .…”

“…In this context, it is also worth noting the necessity of reaching a minimum surface charge density for an optimum biocidal efficiency of cationic surfaces, − either to foster adhesion of bacterial cells on the surfaces or cause leaching of Ca 2+ and Mg 2+ . We found that the loss of stabilizing ions is a key ingredient of surfaces in killing bacteria, as emerged from the fact that films made of copolymers containing crown ether pedants, the latter being introduced with the aim of sequestering alkali-earth ions, were biocidal versus Escherichia coli . Such a result indirectly confirmed the presence of a mechanism of action that starts by leaching or complexing the envelope stabilizing cations.…”

“…We found that the loss of stabilizing ions is a key ingredient of surfaces in killing bacteria, as emerged from the fact that films made of copolymers containing crown ether pedants, the latter being introduced with the aim of sequestering alkali-earth ions, were biocidal versus Escherichia coli. 16 Such a result indirectly confirmed the presence of a mechanism of action that starts by leaching or complexing the envelope stabilizing cations.…”

“…35−37 The latter result is in accordance with previous data reporting the bactericidal activity of surfaces made of polymer containing crown ethers pendants as chelating agents of divalent cations. 16 The cation imbalance also induced a loss of LPS. 38,53 This last hypothesis is supported by the increase in the expression of the biosynthetic genes of the LPS core, waaA and waaC.…”

A redox-responsive macrocycle based on the crown ether C7Te for enhanced bacterial inhibition

“…[20][21][22] Functionalized supramolecular nanomaterials based on crown-ether macrocycles have been utilized in controlling bacterial infections, although research on their antimicrobial activity is limited, and their antimicrobial efficacy falls below that of conventional disinfectants. [23][24][25] Using redox-responsive crownether macrocycles as cofactors for traditional disinfectants may help combat microbial resistance from long-term traditional disinfectant use and substantially enhance the antimicrobial efficiency of crown-ether macrocycles. Drug repurposing, a strategy to identify new applications for approved drugs beyond their original indications, not only reduces research investment and risk but also shortens the timeline of drug discovery and development.…”