Targeted Killing of Pseudomonas aeruginosa by Pyocin G Occurs via the Hemin Transporter Hur.
ATPases Associated with Diverse Cellular Activities
/ genetics
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ genetics
Bacteriocins
/ chemistry
Drug Resistance, Multiple
/ drug effects
Hemin
/ genetics
Humans
Membrane Proteins
/ genetics
Protein Binding
/ drug effects
Pseudomonas Infections
/ drug therapy
Pseudomonas aeruginosa
/ genetics
Pyocins
/ chemistry
FtsH
TonB-dependent transporter
bacteriocin
protein antibiotic
protein import
Journal
Journal of molecular biology
ISSN: 1089-8638
Titre abrégé: J Mol Biol
Pays: Netherlands
ID NLM: 2985088R
Informations de publication
Date de publication:
12 06 2020
12 06 2020
Historique:
received:
06
03
2020
revised:
21
04
2020
accepted:
21
04
2020
pubmed:
28
4
2020
medline:
29
12
2020
entrez:
28
4
2020
Statut:
ppublish
Résumé
Pseudomonas aeruginosa is a priority pathogen for the development of new antibiotics, particularly because multi-drug-resistant strains of this bacterium cause serious nosocomial infections and are the leading cause of death in cystic fibrosis patients. Pyocins, bacteriocins of P. aeruginosa, are potent and diverse protein antibiotics that are deployed during bacterial competition. Pyocins are produced by more than 90% of P. aeruginosa strains and may have utility as last resort antibiotics against this bacterium. In this study, we explore the antimicrobial activity of a newly discovered pyocin called pyocin G (PyoG). We demonstrate that PyoG has broad killing activity against a collection of clinical P. aeruginosa isolates and is active in a Galleria mellonella infection model. We go on to identify cell envelope proteins that are necessary for the import of PyoG and its killing activity. PyoG recognizes bacterial cells by binding to Hur, an outer-membrane TonB-dependent transporter. Both pyocin and Hur interact with TonB1, which in complex with ExbB-ExbD links the proton motive force generated across the inner membrane with energy-dependent pyocin translocation across the outer membrane. Inner-membrane translocation of PyoG is dependent on the conserved inner-membrane AAA+ ATPase/protease, FtsH. We also report a functional exploration of the PyoG receptor. We demonstrate that Hur can bind to hemin in vitro and that this interaction is blocked by PyoG, confirming the role of Hur in hemin acquisition.
Identifiants
pubmed: 32339530
pii: S0022-2836(20)30308-9
doi: 10.1016/j.jmb.2020.04.020
pmc: PMC7322526
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Bacteriocins
0
Membrane Proteins
0
Pyocins
0
tonB protein, Bacteria
0
Hemin
743LRP9S7N
ATPases Associated with Diverse Cellular Activities
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
3869-3880Subventions
Organisme : Wellcome Trust
ID : 201505/Z/16/Z
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.
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