BELIEVE - "Biomimetic antimicrobial vesicle-like nanoarchitectures for multi-drug-resistant bacteria"- PRIN2022 (Prot. 2022HSFEPY)

Community spread of multidrug resistant (MDR) bacteria is a natural phenomenon, amplified by the overuse and inappropriate exposure to different antibiotics. Nowadays, MDR is an important public health threat that must be approached urgently and proactively. The problem of MDR can be further aggravated by the development of biofilm, a cluster of bacterial cells embedded in an extracellular matrix even more resistant to most antibiotics and host defences compared with planktonic-resistant bacterial cells. MDR and associated biofilm infections make the treatment of bacterial diseases by conventional therapeutic strategies a very difficult task. BELIEVE tackles this problem by proposing an innovative strategy to overcome the bacterial resistance mechanism and degrade the biofilm matrix or inhibit its growth. This goal will be achieved by the development of new antimicrobial lipid-based nanoarchitectures able to protect the bioactive function from proteolytic attack, reduce toxicity and enhance activity. This is a central issue in the treatment of MDR since it requires a deep understanding of the structural properties of the bacterial membrane and its interaction with antimicrobial drugs. Tackling this ambitious program requires a wide spectrum of complementary expertise, ranging from the synthesis of polymers, lipids and peptides as building blocks of new amphiphilic antimicrobial molecules, to the design and physico-chemical characterization of self-assembled structures of different nature, as well as skills in isolation and purification of bacterial polysaccharides and molecular and cellular biology and microbial biotechnology, focused on bacterial models. The BELIEVE consortium includes units with all the theoretical and experimental skills necessary to achieve the project goal. Throughout the project, we will explore Extracellular Membrane Vesicles (EMVs) produced by a non-pathogenic bacterium to mimic bacterial membranes and study glycan polymers which play a crucial role in MDR. This study will represent the starting point for the elucidation of the interaction between pathogenic cells and a set of novel amphiphilic molecules with potential, but established, antimicrobial activity. The latter will be synthesized and incorporated into lipid-based vesicle-like nanoarchitectures and validated on selected Gram-negative and Gram-positive bacterial strains, and on their produced biofilm. The proposed approach makes it possible to understand the origin of the physico-chemical features of natural systems at the molecular level, which will enable the development of naturally-inspired effective antimicrobial and anti-biofilm nanostructured systems. We are confident that the fundamental advancements in the strategies to combat bacteria and biofilm-related infections with high application potential as those proposed by BELIEVE could have a huge social and health impact.