Dynamic relocalization of cytosolic type III secretion system components prevents premature protein secretion at low external pH

Stephan Wimmi, Alexander Balinovic, Hannah Jeckel, Lisa Selinger, Dimitrios Lampaki, Emma Eisemann, Ina Meuskens, Dirk Linke, Knut Drescher, Ulrike Endesfelder and Andreas Diepold ()
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Stephan Wimmi: Max Planck Institute for Terrestrial Microbiology
Alexander Balinovic: Max Planck Institute for Terrestrial Microbiology
Hannah Jeckel: Max Planck Institute for Terrestrial Microbiology
Lisa Selinger: Max Planck Institute for Terrestrial Microbiology
Dimitrios Lampaki: Max Planck Institute for Terrestrial Microbiology
Emma Eisemann: Max Planck Institute for Terrestrial Microbiology
Ina Meuskens: University of Oslo
Dirk Linke: University of Oslo
Knut Drescher: Max Planck Institute for Terrestrial Microbiology
Ulrike Endesfelder: Max Planck Institute for Terrestrial Microbiology
Andreas Diepold: Max Planck Institute for Terrestrial Microbiology

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Many bacterial pathogens use a type III secretion system (T3SS) to manipulate host cells. Protein secretion by the T3SS injectisome is activated upon contact to any host cell, and it has been unclear how premature secretion is prevented during infection. Here we report that in the gastrointestinal pathogens Yersinia enterocolitica and Shigella flexneri, cytosolic injectisome components are temporarily released from the proximal interface of the injectisome at low external pH, preventing protein secretion in acidic environments, such as the stomach. We show that in Yersinia enterocolitica, low external pH is detected in the periplasm and leads to a partial dissociation of the inner membrane injectisome component SctD, which in turn causes the dissociation of the cytosolic T3SS components. This effect is reversed upon restoration of neutral pH, allowing a fast activation of the T3SS at the native target regions within the host. These findings indicate that the cytosolic components form an adaptive regulatory interface, which regulates T3SS activity in response to environmental conditions.

Date: 2021
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DOI: 10.1038/s41467-021-21863-4

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