Exploiting the aggregation propensity of beta-lactamases to design inhibitors that induce enzyme misfolding

Previously, the Switch lab showed that peptide-mediated induction of widespread protein aggregation in bacteria is a promising new antimicrobial avenue. These peptides, termed Pept-InsTM, therefore carry promiscuous aggregation prone regions (APRs), seeding (toxic) aggregation of many bacterial proteins. Now, Khodaparast et al. show for the first time that Pept-InsTM can also be exploited to achieve protein (family) specific knockdown in bacteria, similar to what was shown in mammalian cells, by targeting APRs specific to antibiotic resistance factors.

Read the full review here: https://www.nature.com/articles/s41467-023-41191-z