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The type VII secretion system of Staphylococcus aureus secretes a nuclease toxin that targets competitor bacteria

Lookup NU author(s): Dr Guillermina Casabona, Professor Tracy Palmer FRS FRSE FMedSciORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Nature Publishing Group, 2017.

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© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. The type VII protein secretion system (T7SS) plays a critical role in the virulence of human pathogens including Mycobacterium tuberculosis and Staphylococcus aureus. Here, we report that the S. aureus T7SS secretes a large nuclease toxin, EsaD. The toxic activity of EsaD is neutralized during its biosynthesis through complex formation with an antitoxin, EsaG, which binds to its C-terminal nuclease domain. The secretion of EsaD is dependent on a further accessory protein, EsaE, that does not interact with the nuclease domain, but instead binds to the EsaD N-terminal region. EsaE has a dual cytoplasmic/membrane localization, and membrane-bound EsaE interacts with the T7SS secretion ATPase, EssC, implicating EsaE in targeting the EsaDG complex to the secretion apparatus. EsaD and EsaE are co-secreted, whereas EsaG is found only in the cytoplasm and may be stripped off during the secretion process. Strain variants of S. aureus that lack esaD encode at least two copies of EsaG-like proteins, most probably to protect themselves from the toxic activity of EsaD secreted by esaD + strains. In support of this, a strain overproducing EsaD elicits significant growth inhibition against a sensitive strain. We conclude that the T7SS may play unexpected and key roles in bacterial competitiveness.

Publication metadata

Author(s): Cao Z, Casabona MG, Kneuper H, Chalmers JD, Palmer T

Publication type: Article

Publication status: Published

Journal: Nature Microbiology

Year: 2017

Volume: 2

Issue: 1

Online publication date: 10/10/2016

Acceptance date: 26/08/2016

Date deposited: 14/02/2019

ISSN (electronic): 2058-5276

Publisher: Nature Publishing Group


DOI: 10.1038/nmicrobiol.2016.183

PubMed id: 27723728


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Funder referenceFunder name
110183/Z/15/ZWellcome Trust