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Volume 70, Issue 7

Editor's Choice escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5 No Access

Abstract

is an intracellular bacterial pathogen that utilizes a type III secretion apparatus to inject effector proteins into host cells.

The T3SS effector IpaH4.5 is important for the virulence of .

This study aimed to elucidate the molecular mechanism and host target of the IpaH4.5 as well as its roles in infection.

The GAP assay was used to identify substrate Rab GTPases of IpaH4.5. A coimmunoprecipitation assay was applied to identify the interaction of Rab GTPases with IpaH4.5. A confocal microscopy analysis was used to assess the effects of IpaH4.5 on mannose 6-phosphate receptor (MPR) trafficking. To identify the effects of IpaH4.5 GAP activity on the activity of lysosomal cathepsin B, the Magic Red-RR assay was used. Finally, the intracellular persistence assay was used to identify IpaH4.5 GAP activity in intracellular growth.

We found that the effector IpaH4.5 disrupts MPR trafficking and lysosomal function, thereby counteracting host lysosomal degradation. IpaH4.5 harbours TBC-like dual-finger motifs and exhibits potent RabGAP activities towards Rab31. IpaH4.5 disrupts the transport of the cation-dependent mannose 6-phosphate receptor (CD-MPR) from the Golgi to the endosome by targeting Rab31, thereby attenuating lysosomal function. As a result, the intracellular persistence of requires IpaH4.5 TBC-like GAP activity to mediate bacterial escape from host lysosome-mediated elimination.

We identified an unknown function of IpaH4.5 and its potential role in infection.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): infection , IpaH4.5 , Rab31 and Shigella
Funding
This study was supported by the:
  • National Key Research and Development Program of China (Award 2018YFA0900800)
    • Principle Award Recipient: MingxinDong
  • National Natural Science Foundation of China (Award 81671973)
    • Principle Award Recipient: NotApplicable
  • National Natural Science Foundation of China (Award 81773205)
    • Principle Award Recipient: CongwenWei
  • National Natural Science Foundation of China (Award 31670761, 31872715，82070595)
    • Principle Award Recipient: HuiZhong
© 2021 The Authors
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/content/journal/jmm/10.1099/jmm.0.001382
2021-07-23
2024-05-10
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Shigella escapes lysosomal degradation through inactivation of Rab31 by IpaH4.5
J. Med. Microbiol. 70, 001382 (2021); https://doi.org/10.1099/jmm.0.001382
/content/journal/jmm/10.1099/jmm.0.001382
/content/journal/jmm/10.1099/jmm.0.001382
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