Outer membrane translocation of pyocins via the copper regulated TonB-dependent transporter CrtA

Premsuriya, J., Mosbahi, K., Atanaskovic, I., Kleanthous, C. and Walker, D. (2023) Outer membrane translocation of pyocins via the copper regulated TonB-dependent transporter CrtA. Biochemical Journal, 480(14), pp. 1035-1049. (doi: 10.1042/BCJ20220552) (PMID:37399084) (PMCID:PMC10422930)

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Pseudomonas aeruginosa is a common cause of serious hospital-acquired infections, the leading proven cause of mortality in people with cystic fibrosis and is associated with high levels of antimicrobial resistance. Pyocins are narrow-spectrum protein antibiotics produced by P. aeruginosa that kill strains of the same species and have the potential to be developed as therapeutics targeting multi-drug resistant isolates. We have identified two novel pyocins designated SX1 and SX2. Pyocin SX1 is a metal-dependent DNase while pyocin SX2 kills cells through inhibition of protein synthesis. Mapping the uptake pathways of SX1 and SX2 shows these pyocins utilize a combination of the common polysaccharide antigen (CPA) and a previously uncharacterized TonB-dependent transporter (TBDT) PA0434 to traverse the outer membrane. In addition, TonB1 and FtsH are required by both pyocins to energize their transport into cells and catalyze their translocation across the inner membrane, respectively. Expression of PA0434 was found to be specifically regulated by copper availability and we have designated PA0434 as Copper Responsive Transporter A, or CrtA. To our knowledge these are the first S-type pyocins described that utilize a TBDT that is not involved in iron uptake.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Walker, Professor Daniel and Premsuriya, Jiraphan and Mosbahi, Dr Khedidja
Authors: Premsuriya, J., Mosbahi, K., Atanaskovic, I., Kleanthous, C., and Walker, D.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Biochemical Journal
Publisher:Portland Press
ISSN (Online):1470-8728
Published Online:03 July 2023
Copyright Holders:Copyright © 2023 The Authors
First Published:First published in Biochemical Journal 480(14): 1035-1049
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173241Protein Antibiotics: Discovery, mode of action and developmentDaniel WalkerWellcome Trust (WELLCOTR)ALR01040 / 201505/Z/16/ZSII - Bacteriology