DataVXAdvanced SciencePaper
journal article·2026-05Open access

An ATP‐Mediated Antibiotic β‐Peptide Nanofiber That Kills Multidrug‐Resistant Bacteria via a Multistage Mechanism

Sohini Chakraborty, Kamal el Battioui, Dániel Molnár, Bálint Jezsó, Lejla Daruka, Tasvilla Sonallya, Tünde Juhász, Rita Hirmondó, Imola Cs. Szigyártó, Loránd Románszki, Natália Tőkési, Daniel Pinkas, Eszter Házy, Olivér Pavela, Andrea Bodor, Zoltán Varga, István Mándity, Mihály Kovács, Csaba Pál, Kata Horváti, Judit Tóth, Tamás Beke‐Somfai

Advanced Science· Volume 13· Issue 28
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Source abstract

Abstract

ABSTRACT Artificial bioinspired supramolecular assemblies hold great potential to alter modern medicine. Organic tissue‐like nanomaterials built from foldamer peptidomimetics and natural biomolecules could expand our boundaries toward new biocompounds that are able to address global health challenges. Related, antimicrobial resistance against conventional antibiotics motivates search for new compounds with orthogonal mechanisms. Here we designed an antibacterial system where natural adenosine phosphates (APs) trigger supramolecular co‐assemblies from a lipopolysaccharide‐targeting (LPS) antimicrobial β 3 ‐peptide (3K). Cryo‐EM and confocal microscopy images on E. coli confirmed that real‐time action of 3K‐APs progresses via a multiscale mechanism. Initially, entangled nanofibers capture bacteria resulting in agglutination. Further, individual cells become enwrapped, undergoing a reduction in cell height, as observed by AFM. Finally, in situ cryo‐EM observations, offering insight into their structural state in solution, suggest an association between the presence of extracellular vesicles and loss of cell integrity, which may contribute to cell death. 3K‐ATP was tested on multidrug resistant bacterial strains which adapted to membrane‐targeting antibiotics, where only limited cross‐resistance was observed. Resistant strains modifying their LPS even showed increased sensitivity. Besides induced disassembly by target membranes, degradation could also be reached through enzymatic hydrolysis of APs, altogether resulting in supramolecular bactericides with controllable build‐up and clearance.
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Research context

Nanomaterials

OpenAlex topics: Supramolecular Self-Assembly in Materials · Antimicrobial agents and applications · Antimicrobial Peptides and Activities

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Institute of Materials and Environmental Chemistry HUN‐REN Research Centre for Natural Sciences Budapest Hungary

Department of Chemistry, Stella Maris College (Autonomous) University of Madras Chennai Tamil Nadu India

Hevesy György Ph.D. School of Chemistry Eötvös Loránd University Budapest Hungary

Institute of Molecular Life Sciences HUN‐REN Research Centre for Natural Sciences Budapest Hungary

Doctoral School of Biology and Institute of Biology Eötvös Loránd University Budapest Hungary

HUN‐REN‐ELTE Motor Pharmacology Research Group, Department of Biochemistry Eötvös Loránd University Budapest Hungary

Synthetic and Systems Biology Unit Institute of Biochemistry HUN‐REN Biological Research Centre Szeged Szeged H‐6726 Hungary

Cryo‐Electron Microscopy and Tomography Core Facility CEITEC Masarykova University Brno Czech Republic

HUN‐REN‐ELTE Motor Pharmacology Research Group Department of Biochemistry Eötvös Loránd University Budapest Hungary

ELTE Eötvös Loránd University Institute of Chemistry Analytical and BioNMR Laboratory Budapest Hungary

Department of Physical Chemistry and Materials Science, Faculty of Chemical Technology and Biotechnology Budapest University of Technology and Economics Budapest Hungary

Department of Organic Chemistry Faculty of Pharmacy Semmelweis University Budapest Hungary

MTA–HUN‐REN TTK Lendület “Momentum” Peptide‐Based Vaccines Research Group Institute of Materials and Environmental Chemistry HUN‐REN Research Centre for Natural Sciences Budapest Hungary

Funding

National Research, Development and Innovation Office · H2020 European Research Council

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