Phylogenetic Classification and Functional Review of Autotransporters

Kaitlin R. Clarke, Lilian Hor, Akila Pilapitiya, Joen Luirink, Jason J. Paxman*, Begoña Heras

*Corresponding author for this work

Research output: Contribution to JournalReview articleAcademicpeer-review


Autotransporters are the core component of a molecular nano-machine that delivers cargo proteins across the outer membrane of Gram-negative bacteria. Part of the type V secretion system, this large family of proteins play a central role in controlling bacterial interactions with their environment by promoting adhesion to surfaces, biofilm formation, host colonization and invasion as well as cytotoxicity and immunomodulation. As such, autotransporters are key facilitators of fitness and pathogenesis and enable co-operation or competition with other bacteria. Recent years have witnessed a dramatic increase in the number of autotransporter sequences reported and a steady rise in functional studies, which further link these proteins to multiple virulence phenotypes. In this review we provide an overview of our current knowledge on classical autotransporter proteins, the archetype of this protein superfamily. We also carry out a phylogenetic analysis of their functional domains and present a new classification system for this exquisitely diverse group of bacterial proteins. The sixteen phylogenetic divisions identified establish sensible relationships between well characterized autotransporters and inform structural and functional predictions of uncharacterized proteins, which may guide future research aimed at addressing multiple unanswered aspects in this group of therapeutically important bacterial factors.

Original languageEnglish
Article number921272
Pages (from-to)1-20
Number of pages20
JournalFrontiers in Immunology
Issue numberJuly
Early online date1 Jul 2022
Publication statusPublished - Jul 2022

Bibliographical note

Funding Information:
We acknowledge the support of the Australian Research Council, the National Health and Medical Research Council, The Amsterdam Institute of Molecular and Life Sciences (Vrije Universiteit), and the La Trobe Institute for Molecular Science (La Trobe University).

Funding Information:
This work was supported by the Australian Research Council (ARC) project grants (DP180102987, DP210100673), a National Health and Medical Research Council (NHMRC) Project Grant (GNT1143638) and an La Trobe Strategic Innovation Fund project.

Publisher Copyright:
Copyright © 2022 Clarke, Hor, Pilapitiya, Luirink, Paxman and Heras.


  • adhesins
  • bacterial pathogenesis
  • secreted proteins
  • toxins
  • type V secretion system
  • virulence


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