Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport

Behrens, H. M. et al. (2020) Pyocin S5 import into Pseudomonas aeruginosa reveals a generic mode of bacteriocin transport. mBio, 11(2), e03230-19. (doi: 10.1128/mBio.03230-19) (PMID:32156826) (PMCID:PMC7064778)

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Pyocin S5 (PyoS5) is a potent protein bacteriocin that eradicates the human pathogen Pseudomonas aeruginosa in animal infection models, but its import mechanism is poorly understood. Here, using crystallography, biophysical and biochemical analyses, and live-cell imaging, we define the entry process of PyoS5 and reveal links to the transport mechanisms of other bacteriocins. In addition to its C-terminal pore-forming domain, elongated PyoS5 comprises two novel tandemly repeated kinked 3-helix bundle domains that structure-based alignments identify as key import domains in other pyocins. The central domain binds the lipid-bound common polysaccharide antigen, allowing the pyocin to accumulate on the cell surface. The N-terminal domain binds the ferric pyochelin transporter FptA while its associated disordered region binds the inner membrane protein TonB1, which together drive import of the bacteriocin across the outer membrane. Finally, we identify the minimal requirements for sensitizing Escherichia coli toward PyoS5, as well as other pyocins, and suggest that a generic pathway likely underpins the import of all TonB-dependent bacteriocins across the outer membrane of Gram-negative bacteria.

Item Type:Articles
Additional Information:This work was supported by the Wellcome Trust through the Infection, Immunology and Translational Medicine DPhil studentship to H.M.B. and through a Collaborative Award to C.K. and D.W. T.M.W. was supported by the Erasmus scheme of the European Commission. C.V.R. is funded by a Wellcome Trust Investigator Award (104633/Z/14/Z), an ERC Advanced Grant ENABLE (641317), and an MRC Program Grant (MR/N020413/1). J.G. acknowledges support of a Junior Research Fellowship from The Queen’s College, Oxford. P. aeruginosa mutant library strain PW8161 was created with support of grant NIH P30 DK089507.
Glasgow Author(s) Enlighten ID:Thompson, Catriona and Walker, Professor Daniel
Authors: Behrens, H. M., Lowe, E. D., Gault, J., Housden, N. G., Kaminska, R., Weber, T. M., Thompson, C. M.A., Mislin, G. L.A., Schalk, I. J., Walker, D., Robinson, C. V., and Kleanthous, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN (Online):2150-7511
Copyright Holders:Copyright © 2020 Behrens et al.
First Published:First published in mBio 11(2):e03230-19
Publisher Policy:Reproduced under a Creative Commons licence

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