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Updated: Nov 21, 2025

Extraction and Visualization of Protein Aggregates after Treatment of Escherichia coli with a Proteotoxic Stressor
Published on: June 29, 2021
Investigating the mechanism of action of aggregation-inducing antimicrobial Pept-ins
Guiqin Wu1, Laleh Khodaparast1, Ladan Khodaparast1
1Switch Laboratory, VIB Center for Brain and Disease Research, Herestraat 49, 3000 Leuven, Belgium; Switch Laboratory, Department of Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000 Leuven, Belgium.
Abstract:
Aggregation can be selectively induced by aggregation-prone regions (APRs) contained in the target proteins. Aggregation-inducing antimicrobial peptides (Pept-ins) contain sequences homologous to APRs of target proteins and exert their bactericidal effect by causing aggregation of a large number of proteins. To better understand the mechanism of action of Pept-ins and the resistance mechanisms, we analyzed the phenotypic, lipidomic, and transcriptomic as well as genotypic changes in laboratory-derived Pept-in-resistant E. coli mutator cells. The analysis showed that the Pept-in resistance mechanism is dominated by a decreased Pept-in uptake, in both laboratory-derived mutator cells and clinical isolates. Our data indicate that Pept-in uptake involves an electrostatic attraction between the Pept-in and the bacterial membrane and follows a complex mechanism potentially involving many transporters. Furthermore, it seems more challenging for bacteria to become resistant toward Pept-ins that are less dependent on electrostatic attraction for uptake, suggesting that future Pept-ins should be selected for this property.
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