The C. difficile toxin B membrane translocation machinery is an evolutionarily conserved protein delivery apparatus

Kathleen E. Orrell, Michael J. Mansfield, Andrew C. Doxey and Roman A. Melnyk ()
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Kathleen E. Orrell: The Hospital for Sick Children Research Institute
Michael J. Mansfield: University of Waterloo
Andrew C. Doxey: University of Waterloo
Roman A. Melnyk: The Hospital for Sick Children Research Institute

Nature Communications, 2020, vol. 11, issue 1, 1-11

Abstract: Abstract Large Clostridial Toxins (LCTs) are a family of six homologous protein toxins that are implicated in severe disease. LCTs infiltrate host cells using a translocation domain (LCT-T) that contains both cell-surface receptor binding sites and a membrane translocation apparatus. Despite much effort, LCT translocation remains poorly understood. Here we report the identification of 1104 LCT-T homologs, with 769 proteins from bacteria outside of clostridia. Sequences are widely distributed in pathogenic and host-associated species, in a variety of contexts and architectures. Consistent with these homologs being functional toxins, we show that a distant LCT-T homolog from Serratia marcescens acts as a pH-dependent translocase to deliver its effector into host cells. Based on evolutionary footprinting of LCT-T homologs, we further define an evolutionarily conserved translocase region that we show is an autonomous translocase capable of delivering heterologous cargo into host cells. Our work uncovers a broad class of translocating toxins and provides insights into LCT translocation.

Date: 2020
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14306-z

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DOI: 10.1038/s41467-020-14306-z

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