Inhibitors targeting BamA in gram-negative bacteria.
Antibiotics
BamA
Gram-negative bacteria
Outer membrane proteins
β-Barrel protein folding
Journal
Biochimica et biophysica acta. Molecular cell research
ISSN: 1879-2596
Titre abrégé: Biochim Biophys Acta Mol Cell Res
Pays: Netherlands
ID NLM: 101731731
Informations de publication
Date de publication:
01 2024
01 2024
Historique:
received:
05
04
2022
revised:
08
06
2023
accepted:
19
09
2023
medline:
20
11
2023
pubmed:
19
10
2023
entrez:
18
10
2023
Statut:
ppublish
Résumé
Antibiotic resistance has led to an increase in the number of patient hospitalizations and deaths. The situation for gram-negative bacteria is especially dire as the last new class of antibiotics active against these bacteria was introduced to the clinic over 60 years ago, thus there is an immediate unmet need for new antibiotic classes able to overcome resistance. The outer membrane, a unique and essential structure in gram-negative bacteria, contains multiple potential antibacterial targets including BamA, an outer membrane protein that folds and inserts transmembrane β-barrel proteins. BamA is essential and conserved, and its outer membrane location eliminates a barrier that molecules must overcome to access this target. Recently, antibacterial small molecules, natural products, peptides, and antibodies that inhibit BamA activity have been reported, validating the druggability of this target and generating potential leads for antibiotic development. This review will describe these BamA inhibitors, highlight their key attributes, and identify challenges with this potential target.
Identifiants
pubmed: 37852326
pii: S0167-4889(23)00182-9
doi: 10.1016/j.bbamcr.2023.119609
pii:
doi:
Substances chimiques
Escherichia coli Proteins
0
Bacterial Outer Membrane Proteins
0
Anti-Bacterial Agents
0
BamA protein, E coli
0
Types de publication
Review
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
119609Informations de copyright
Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Steven T. Rutherford reports financial support was provided by Genentech Inc. Kelly M. Storek reports financial support was provided by Genentech Inc. Dawei Sun reports financial support was provided by Genentech Inc. Steven T. Rutherford reports a relationship with Genentech Inc. that includes: employment. Kelly M. Storek reports a relationship with Genentech Inc. that includes: employment. Dawei Sun reports a relationship with Genentech Inc. that includes: employment. All authors on this manuscript are employees of Genentech, Inc., a member of the Roche Group, and shareholders in Roche. Genentech, Inc. had no role in the preparation or content of this work or the decision to submit it for publication.