Host manipulation by bacterial type III and type IV secretion system effector proteases

Flavia Viana, Shruthi Sachidanandan Peringathara, Arshad Rizvi, Gunnar N. Schroeder*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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Proteases are powerful enzymes, which cleave peptide bonds, leading most of the time to irreversible fragmentation or degradation of their substrates. They therefore control many critical cell fate decisions in eukaryotes. Bacterial pathogens exploit this power and deliver proteases effectors through specialized secretion systems into host cells. Research over the past years revealed that the functions of protease effectors during infection are diverse, reflecting the lifestyles and adaptations to specific hosts; however, only a small number of peptidase families seem to have given rise to most of these protease virulence factors by the evolution of different substrate-binding specificities, intracellular activation and subcellular targeting mechanisms. Here, we review our current knowledge about the enzymology and function of protease effectors, which Gram-negative bacterial pathogens translocate via type III and IV secretion systems to irreversibly manipulate host processes. We highlight emerging concepts such as signaling by protease cleavage products and effector-triggered immunity (ETI), which host cells employ to detect and defend themselves against a protease attack.
Original languageEnglish
JournalCellular Microbiology
Early online date14 Aug 2021
Publication statusEarly online date - 14 Aug 2021

Bibliographical note

Funding Information:
Protein cartoons were created with the program “Illustrate” (Goodsell, Autin, & Olson, 2019 ). This work was supported by the Medical Research Council UK grant MR/R010552/1.

Publisher Copyright:
© 2021 The Authors. Cellular Microbiology published by John Wiley & Sons Ltd.

Copyright 2021 Elsevier B.V., All rights reserved.


  • Effectors
  • bacterial pathogenesis
  • host-pathogen interaction
  • infection
  • proteases
  • proteolysis
  • type III secretion system (T3SS)
  • type IV secretion system (T4SS)


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