Advanced nanomaterials to target genomic and Z-DNA for bacterial biofilm eradication

ongoing

BactEradiX aims to develop the first-in-class advanced antimicrobial nanomaterial to target biofilm Z-DNA and genomic DNA, to eradicate biofilm and resolve chronic/recalcitrant infections. Infective diseases and antimicrobial resistance are a threat to global health and development. Biofilm formation is a major cause of treatment failure, infection recurrence and acquired resistance development. WHO has declared antimicrobial resistance one of the top 10 global public health threats facing humanity. Infective diseases are an increasingly dramatic problem because the development of new antimicrobials is being slowed down dramatically and drug-resistant bacteria are growing. BactEradiX addresses this urgent global threat by leveraging breakthrough discoveries and advanced lipid-based nanocarrier technologies to target Z-DNA to destabilize the biofilm and to cleave bacterial genomic DNA to kill bacteria. The project seeks to overcome the challenges posed by bacteria in biofilms and the slow pace of development of new antimicrobial strategies. BactEradiX aims at developing a modular and tunable antimicrobial nanoplatform by focusing on two WHO priority bacterial strains: methicillin-resistant S. aureus (MRSA) and multidrug resistant P. aeruginosa. Our specific goals include: (1) characterization of structural Z-DNA in biofilms, (2) design of Z-DNA targeting PNAs for (3) lipid nanoparticles decoration to target and destabilize the biofilm, (4) design and develop antimicrobial anti-gene PNAs able to cleave genomic DNA and block bacterial replication (leading to bacterial death), and (5) validation of tailorable advanced nanomaterial for biofilm eradication: functionality and biocompatibility. The long-term vision of BactEradiX project is to develop the first-in-class modular nanoplatfom for the tailored design of advanced antimicrobial nanomaterials that can ensure a long-term solution for the treatment of chronic and recalcitrant infections.