(Anti-AMR) Advanced Therapeutic Ionic Nanomaterials to Combat Resistant Bacterial Infections

What is Anti-AMR about?

β-Lactam antibiotics, like penicillin, are “miracle drugs” that represent the most prescribed antibiotic class worldwide. Unfortunately, due to their extensive use, the resistance against these drugs is on the rise. Here, the teams proposes to test ionic β-lactam (nano)materials as next-generation therapeutics against critical Gram-negative bacterial pathogens (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii).

In particular, the team will assess the efficacy and investigate the mechanism of action of diverse β-lactam compounds administered in combination with functionalized silica nanoparticles, already synthesized by the Portuguese research team. It will leverage well-defined antibiotic-sensitive and -resistant laboratory strains developed at UT Austin, alongside characterized clinical isolates and an insect infection model to explore the potential of combining two drug modalities (ionic pharmaceutical formulations and mesoporous silica nanoparticles) that have independently shown great promise in the field of drug delivery.

What critical challenges is Anti-AMR addressing?

The surge of antimicrobial resistance (AMR) poses formidable challenges to global health. In numbers, 1.3 million deaths per year are directly attributable to AMR and 10 million deaths per year due to AMR are projected by 2050. While 65% of globally prescribed antibiotics are β-lactam drugs like penicillin, because of their extensive use, 70% of deaths attributable to AMR are due to β-lactam resistance. β-Lactam antibiotics are “miracle drugs” with broad activity against bacterial pathogens and unmatched safety profiles for human consumption. For this reason, it is important to develop novel effective strategies that will increase their efficacy and prolong their use.

How will Anti-AMR address antimicrobial resistance?

The team will combine two materials that have shown promise in the field of drug delivery, ionic pharmaceutical formulations and mesoporous silica nanoparticles, with invaluable β-lactam antibiotics. These combinations will be tested against defined laboratory model strains, as well as multidrug-resistant clinical isolates as novel next-generation therapies against antibiotic-resistant pathogens. While such materials have never been tested before as resistant breakers, our proposed efforts will become possible through the interdisciplinary collaboration between teams, with combined expertise in supramolecular and pharmaceutical chemistry, clinical microbiology and antibiotic resistance.

How is Anti-AMR contributing to increase the efficacy of β-lactam compounds?

By the end of the funding period, the team will have thoroughly tested the efficacy of 10 novel β-lactam / functionalized silica nanoparticle combinations against 4 high-priority Gram-negative bacterial pathogens, across several antibiotic-susceptible and-resistant strains. Considering the novelty of this approach, the proposed work will provide a comprehensive evaluation of the potential of such therapeutic combinations for the treatment of critical pathogens.