Targeted interplay between bacterial pathogens and host autophagy

Padhmanand Sudhakar, Anne Claire Jacomin, Isabelle Hautefort, Siva Samavedam, Koorosh Fatemian, Eszter Ari, Leila Gul, Amanda Demeter, Emily Jones, T. Korcsmáros, Ioannis P. Nezis

Research output: Contribution to journalArticle

Abstract

Due to the critical role played by autophagy in pathogen clearance, pathogens have developed diverse strategies to subvert it. Despite previous key findings of bacteria-autophagy interplay, asystems-level insight into selective targeting by the host and autophagy modulation by the pathogens is lacking. We predicted potential interactions between human autophagy proteins and effector proteins from 56 pathogenic bacterial species by identifying bacterial proteins predicted to have recognition motifs for selective autophagy receptors SQSTM1/p62, CALCOCO2/NDP52 and MAP1LC3/LC3. Using structure-based interaction prediction, we identified bacterial proteins capable to modify core autophagy components. Our analysis revealed that autophagy receptors in general potentially target mostly genus-specific proteins, and not those present in multiple genera. The complementarity between the predicted SQSTM1/p62 and CALCOCO2/NDP52 targets, which has been shown for Salmonella, Listeria and Shigella, could be observed across other pathogens. This complementarity potentially leaves the host more susceptible to chronic infections upon the mutation of autophagy receptors. Proteins derived from enterotoxigenic and non-toxigenic Bacillus outer membrane vesicles indicated that autophagy targets pathogenic proteins rather than non-pathogenic ones. We also observed apathogen-specific pattern as to which autophagy phase could be modulated by specific genera. We found intriguing examples of bacterial proteins that could modulate autophagy, and in turn being targeted by autophagy as ahost defense mechanism. We confirmed experimentally an interplay between a Salmonella protease, YhjJ and autophagy. Our comparative meta-analysis points out key commonalities and differences in how pathogens could affect autophagy and how autophagy potentially recognizes these pathogenic effectors. Abbreviations: ATG5: autophagy related 5; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; GST: glutathione S-transferase; LIR: MAP1LC3/LC3-interacting region; MAP1LC3/LC3: microtubule associated protein 1 light chain 3 alpha; OMV: outer membrane vesicles; SQSTM1/p62: sequestosome 1; SCV: Salmonella containing vesicle; TECPR1: tectonin beta-propeller repeat containing 1; YhjJ: hypothetical zinc-protease.

Original languageEnglish
JournalAutophagy
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Autophagy
Bacterial Proteins
Proteins
Microtubule-Associated Proteins
Membranes
Glutathione Transferase
Salmonella
Zinc

Keywords

  • Autophagy
  • bacterial regulation of host
  • CALCOCO2/NDP52
  • interplay
  • MAP1LC3/LC3
  • MAP1LC3/LC3-interacting region motif
  • microbiota
  • pathogen recognition
  • SQSTM1/p62

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Sudhakar, P., Jacomin, A. C., Hautefort, I., Samavedam, S., Fatemian, K., Ari, E., ... Nezis, I. P. (2019). Targeted interplay between bacterial pathogens and host autophagy. Autophagy. https://doi.org/10.1080/15548627.2019.1590519

Targeted interplay between bacterial pathogens and host autophagy. / Sudhakar, Padhmanand; Jacomin, Anne Claire; Hautefort, Isabelle; Samavedam, Siva; Fatemian, Koorosh; Ari, Eszter; Gul, Leila; Demeter, Amanda; Jones, Emily; Korcsmáros, T.; Nezis, Ioannis P.

In: Autophagy, 01.01.2019.

Research output: Contribution to journalArticle

Sudhakar, P, Jacomin, AC, Hautefort, I, Samavedam, S, Fatemian, K, Ari, E, Gul, L, Demeter, A, Jones, E, Korcsmáros, T & Nezis, IP 2019, 'Targeted interplay between bacterial pathogens and host autophagy', Autophagy. https://doi.org/10.1080/15548627.2019.1590519
Sudhakar P, Jacomin AC, Hautefort I, Samavedam S, Fatemian K, Ari E et al. Targeted interplay between bacterial pathogens and host autophagy. Autophagy. 2019 Jan 1. https://doi.org/10.1080/15548627.2019.1590519
Sudhakar, Padhmanand ; Jacomin, Anne Claire ; Hautefort, Isabelle ; Samavedam, Siva ; Fatemian, Koorosh ; Ari, Eszter ; Gul, Leila ; Demeter, Amanda ; Jones, Emily ; Korcsmáros, T. ; Nezis, Ioannis P. / Targeted interplay between bacterial pathogens and host autophagy. In: Autophagy. 2019.
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