Nanocapsule designs for antimicrobial resistance

Abstract

The pressing need of new antimicrobial products is growing stronger, particularly because of widespread antimicrobial resistance, endangering our ability to treat common infections.The recent coronavirus pandemic has dramatically highlighted the...

Virus-inspired designs of antimicrobial nanocapsules

“…The designed AM capsule displays properties of higher porosity and flexibility that may make it more amenable to interact with and disrupt the membrane when compared with the double layer antimicrobial capsule we studied previously. 4,5,18 These properties were tested by placing the AM-β -annulus near a model bacterial membrane constituted by POPC and POPS lipids (in ratio 3:1). 5 During the course of the unrestrained simulation, the capsule moves towards the membrane and starts to interact with it at around 1 µs, as shown by the number of protein-membrane contacts as a function of the time (Figure 8).…”

“…We used the recent lipid parametrisation in the SIRAH force field 20 united with its characteristic medium grained resolution between the atomistic and the MARTINI coarse-grained one, 19 for the simulations of antimicrobial capsules on membranes (as reported in our previous work.) 5 For the simulation of the capsules on membranes, POPC and POPS (in ratio 3:1) were selected among the SIRAH available lipids, as POPC is zwitterionic and POPS is negatively charged, reflecting the characteristics of the DLPC and DLPG lipid used in other force-fields for representing the microbial membrane.…”

“…One of the best nature-designed gene delivery system is represented by viruses, as they have evolved a number of efficient mechanisms to penetrate cell membranes and implement effective processes to transfer their genomic material to targeted cells. Recently, we have shown that engineered virus-like nanocapsules derived from synthetic multi branched peptides are able to promote bacterial membrane poration and are, at the same time, suitable for gene delivery 4,5 .…”

“…In particular, it has promoted the modification of existing compounds to escape the resistance developed by bacteria. 6 One crucial aspect in the efficacy of antimicrobials is their interaction and recognition of the cellular membrane and their ability to selectively perturb microbial versus mammalian membrane integrity 5 . Therefore in modelling such interactions is very important to select the right lipid composition mixture and to fine-tune and characterise the specific peptide-lipid interactions.…”

“…We have previously described some of these engineered AM nanocapsules, 4,5,18 here we want to describe a protocol to design a self-assembling nanocapsule inspired to the Tomato Bushy Structure by extracting some essential building blocks that infer the fullerene geometry and functionalise them with peptides that carry the AM activity.…”