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Novel antimicrobial agents inhibiting lipid II incorporation into peptidoglycan

Nijland, Mark (2019) Novel antimicrobial agents inhibiting lipid II incorporation into peptidoglycan. Master's Thesis / Essay, Molecular Biology and Biotechnology (2016-2019).


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Antibiotic resistance development in bacteria towards the currently available antibiotics forms a global health threat. Moreover, the antibiotic pipeline is running dry due to the limited success of the conventional culture-based method to introduce novel antibiotics. Innovative platforms have been established that greatly expand the natural product source from which novel antimicrobial compounds can be discovered. Here we focus on five recently identified antimicrobials that were mainly revealed by the application of such platforms. The mode of action of these antimicrobials involve the inhibition of peptidoglycan synthesis by either targeting lipid II (teixobactin, tridecaptin and malacidin) or the recently identified lipid II flippase MurJ (humimycin and LysM). In both cases, lipid II is sequestered from the penicillin binding proteins, thereby preventing synthesis of the peptidoglycan layer, which is fatal for the cell. These compounds are mainly effective against Gram-positive bacteria, with the exception of tridecaptin, and reveal robustness towards resistance development in vitro. The latter is an important feature that make them interesting potential candidates for therapeutic applications.

Item Type: Thesis (Master's Thesis / Essay)
Supervisor name: Scheffers, D.J.
Degree programme: Molecular Biology and Biotechnology (2016-2019)
Thesis type: Master's Thesis / Essay
Language: English
Date Deposited: 31 Jul 2019
Last Modified: 01 Aug 2019 07:57

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