Empowering Antibiotics In The Amr Landscape: Insights From Dendrimer Conjugation In Ali Systems

Laura Daniela Martinenghi*, Tim Van den Nobelen, Jørn Bolstad Christensen, Søren Molin, Helle Krogh Johansen, Jørgen J. Leisner

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingConference abstract in proceedingsResearchpeer-review

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Abstract

In the shadow of the AMR crisis, reigniting the antibiotic pipeline has emerged as a pivotal strategy. Despite the urgent need, there has been a decrease in finding new types of natural or synthetic antibiotics over the past forty years. Of the 65 antibiotics introduced in the last two decades, only four were genuinely new pharmacological classes, whilst the remainder were merely derivatives or modifications of pre-existing compounds. This challenge arises from the need to bypass bacterial resistance, which, paradoxically, is also the target.

Inspired by a 2006 study that successfully integrated propranolol with a known drug delivery polymer, DAB-PAMAM dendrimer, for enhanced cellular uptake, we advanced this approach by conjugating the antibiotic ciprofloxacin with PAMAM dendrimers. This strategy aims to enhance the antibiotic’s effectiveness by preventing its ejection from cells.

The screening results were promising as Escherichia coli showed MIC values of 1.25 µg/µl and Pseudomonas aeruginosa 1-2 µg/µl. Staphylococcus aureus exhibited values, oscillating between 2-4 µg/µl. MIC values, which lowered by a factor of 2 when tested in media other than MHB. The compounds did not result in cytotoxicity nor hemolysis.

An important outcome of these experiments was the insight that tackling AMR requires not only identification of suitable candidates, but also require that standardized screening methodologies are in congruence with clinical needs. Therefore, we employed an air-liquid interface (ALI) culture set-up to mimic respiratory epithelial cells’ natural environment. By introducing P. aeruginosa, a severe cause of respiratory infections, we sought to compare its behavior with standard lab screenings, aiming to bridge the gap between conventional lab methods and clinical needs inside the antimicrobial development pipeline.
Original languageEnglish
Title of host publicationThe Danish Microbiological Society Annual Congress 2023 : Abstract book
Number of pages1
PublisherDanish Microbiological Society
Publication date2023
Pages58-58
Article number56
Publication statusPublished - 2023
EventThe Danish Microbiological Society Annual Congress 2023 - Copenhagen, Denmark
Duration: 13 Nov 202313 Nov 2023

Conference

ConferenceThe Danish Microbiological Society Annual Congress 2023
Country/TerritoryDenmark
CityCopenhagen
Period13/11/202313/11/2023

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