Authors:

Jesus Noriega

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About Paper:

The world is facing a global health crisis as antimicrobial resistance has decreased the effectiveness of current antibiotics. Both gram-negative and gram-positive bacteria have defense mechanisms against most antibiotics. However, the outer membrane (OM) of gram-negative prevents antibacterial compounds from reaching their intracellular targets and hinders the discovery of new antibiotics. The OM is composed of outer membrane proteins (OMPs) which serve as unique virulence factors, making them promising targets for new therapeutics. One such target is the beta-barrel assembly machinery (BAM) complex, which itself is responsible for OMP biogenesis. In E. coli, the BAM complex is composed of five components, BamA-E. BamA is the central and essential component of the complex and is highly conserved among gram-negative bacteria, making it a promising target for the discovery of new antibiotics. Recently, a new inhibitor called darobactin A was found to bind to the barrel domain of BamA and block substrate binding. In this project, we are characterizing an in silico designed stapled peptide called X2W7, which has also been shown to inhibit BAM-mediated OMP biogenesis in MIC assays. The goal of this study is to determine the cryo-EM structure of E. coli BAM in complex with X2W7, which will enhance our understanding of the peptide's binding properties and potential as a drug target. The long-term goal is to determine the effectiveness of X2W7 against bacteria listed by the WHO as critical and urgently needing new antibiotics due to multidrug resistance. Keywords: [no keywords provided]

Source:

Purdue University / 2024

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No topics listed

Co-authors:

Jesus Noriega