Targeted interplay between bacterial pathogens and host autophagy

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.

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Author Sudhakar, Padhmanand
Last Updated November 20, 2019, 16:52 (UTC)
Created August 1, 2019, 10:27 (UTC)
Article Host Type publisher
Article Is Open Access true
Article License Type
Article Version Type publishedVersion
Citation Report https://scite.ai/reports/10.1080/15548627.2019.1590519
DOI 10.1080/15548627.2019.1590519
Date Last Updated 2019-07-16T09:23:16.971048
Evidence open (via free pdf)
Funder code(s) Biotechnology and Biological Sciences Research Council (BB/L006324/1, BB/P007856/1, BB/J004529/1, BB/P016774/1)
Journal Is Open Access false
Open Access Status bronze
PDF URL https://www.tandfonline.com/doi/pdf/10.1080/15548627.2019.1590519?needAccess=true
Publisher URL https://doi.org/10.1080/15548627.2019.1590519