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Targeting bacterial Dsb proteins for the development of anti-virulence agents

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posted on 2023-03-29, 23:35 authored by RP Smith, Jason PaxmanJason Paxman, MJ Scanlon, Begona HerasBegona Heras

Abstract: Recent years have witnessed a dramatic increase in bacterial antimicrobial resistance and a decline in the development of novel antibiotics. New therapeutic strategies are urgently needed to combat the growing threat posed by multidrug resistant bacterial infections. The Dsb disulfide bond forming pathways are potential targets for the development of antimicrobial agents because they play a central role in bacterial pathogenesis. In particular, the DsbA/DsbB system catalyses disulfide bond formation in a wide array of virulence factors, which are essential for many pathogens to establish infections and cause disease. These redox enzymes are well placed as antimicrobial targets because they are taxonomically widespread, share low sequence identity with human proteins, and many years of basic research have provided a deep molecular understanding of these systems in bacteria. In this review, we discuss disulfide bond catalytic pathways in bacteria and their significance in pathogenesis. We also review the use of different approaches to develop inhibitors against Dsb proteins as potential anti-virulence agents, including fragment-based drug discovery, high-throughput screening and other structure-based drug discovery methods.

Funding

This work was supported by Australian Research Council (ARC) grant (DP150102287) and the Australian National Health and Medical Research Council (NHMRC) grant (APP1099151). BH is supported by an Australian Research Council Future Fellowship (FT130100580). RS is supported by an Australian Postgraduate Award (APA) scholarship.

History

Publication Date

2016-07-16

Journal

Molecules

Volume

21

Issue

7

Article Number

811

Pagination

15p.

Publisher

MDPI

ISSN

1420-3049

Rights Statement

© 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).

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