Structure of the Helicobacter pylori Cag Type IV secretion system
- University of Michigan, United States
- Vanderbilt University School of Medicine, United States
Abstract
Bacterial type IV secretion systems (T4SSs) are molecular machines that can mediate interbacterial DNA transfer through conjugation and delivery of effector molecules into host cells. The Helicobacter pylori Cag T4SS translocates CagA, a bacterial oncoprotein, into gastric cells, contributing to gastric cancer pathogenesis. We report the structure of a membrane-spanning Cag T4SS complex, which contains three sub-complexes: a 14-fold symmetric outer membrane core complex (OMCC), 17-fold symmetric periplasmic ring complex (PRC), and stalk domain. Features that differ markedly from those of prototypical T4SSs include an expanded OMCC and unexpected symmetry mismatch between the OMCC and PRC. This structure is one of the largest bacterial secretion system complexes ever reported and illustrates the remarkable structural diversity that exists among bacterial T4SSs.
Data availability
The cryo-EM volumes have been deposited in the Electron Microscopy Data Bank under accession codes EMD-20023 (T4SS C1 reconstruction), EMD-20020 (Focused OMCC Reconstruction), EMD-20022 (OMCC Asymmetric Reconstruction), EMD-20021 (Focused PRC Reconstruction). Map coordinates have been deposited in the Protein Data Bank under accession numbers 6OEE (CagT), 6OEG (CagX), and 6ODI (CagY), 6OEF (O-layer), 6OEH (I-Layer), and 6ODJ (PRC).
-
T4SS C1 reconstructionElectron Microscopy Data Bank, EMD-20023.
-
Focused OMCC ReconstructionElectron Microscopy Data Bank, EMD-20020.
-
OMCC Asymmetric ReconstructionElectron Microscopy Data Bank, EMD-20022.
-
Focused PRC ReconstructionElectron Microscopy Data Bank, EMD-20021.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (AI118932)
- Timothy L Cover
- Melanie D Ohi
National Cancer Institute (CA116087)
- Timothy L Cover
Department of Veterans' Affairs (1I01BX004447)
- Timothy L Cover
National Institute of General Medical Sciences (GM103310)
- Melanie D Ohi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2019, Chung et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 8,922
- views
-
- 925
- downloads
-
- 82
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Structure of the Helicobacter pylori Cag Type IV secretion system
eLife 8:e47644.
https://doi.org/10.7554/eLife.47644
Further reading
-
- Microbiology and Infectious Disease
Mycobacterium tuberculosis’s (Mtb) autarkic lifestyle within the host involves rewiring its transcriptional networks to combat host-induced stresses. With the help of RNA sequencing performed under various stress conditions, we identified that genes belonging to Mtb sulfur metabolism pathways are significantly upregulated during oxidative stress. Using an integrated approach of microbial genetics, transcriptomics, metabolomics, animal experiments, chemical inhibition, and rescue studies, we investigated the biological role of non-canonical L-cysteine synthases, CysM and CysK2. While transcriptome signatures of RvΔcysM and RvΔcysK2 appear similar under regular growth conditions, we observed unique transcriptional signatures when subjected to oxidative stress. We followed pool size and labelling (34S) of key downstream metabolites, viz. mycothiol and ergothioneine, to monitor L-cysteine biosynthesis and utilization. This revealed the significant role of distinct L-cysteine biosynthetic routes on redox stress and homeostasis. CysM and CysK2 independently facilitate Mtb survival by alleviating host-induced redox stress, suggesting they are not fully redundant during infection. With the help of genetic mutants and chemical inhibitors, we show that CysM and CysK2 serve as unique, attractive targets for adjunct therapy to combat mycobacterial infection.
-
- Microbiology and Infectious Disease
- Physics of Living Systems
Filamentous multicellular cable bacteria perform centimeter-scale electron transport in a process that couples oxidation of an electron donor (sulfide) in deeper sediment to the reduction of an electron acceptor (oxygen or nitrate) near the surface. While this electric metabolism is prevalent in both marine and freshwater sediments, detailed electronic measurements of the conductivity previously focused on the marine cable bacteria (Candidatus Electrothrix), rather than freshwater cable bacteria, which form a separate genus (Candidatus Electronema) and contribute essential geochemical roles in freshwater sediments. Here, we characterize the electron transport characteristics of Ca. Electronema cable bacteria from Southern California freshwater sediments. Current–voltage measurements of intact cable filaments bridging interdigitated electrodes confirmed their persistent conductivity under a controlled atmosphere and the variable sensitivity of this conduction to air exposure. Electrostatic and conductive atomic force microscopies mapped out the characteristics of the cell envelope’s nanofiber network, implicating it as the conductive pathway in a manner consistent with previous findings in marine cable bacteria. Four-probe measurements of microelectrodes addressing intact cables demonstrated nanoampere currents up to 200 μm lengths at modest driving voltages, allowing us to quantify the nanofiber conductivity at 0.1 S/cm for freshwater cable bacteria filaments under our measurement conditions. Such a high conductivity can support the remarkable sulfide-to-oxygen electrical currents mediated by cable bacteria in sediments. These measurements expand the knowledgebase of long-distance electron transport to the freshwater niche while shedding light on the underlying conductive network of cable bacteria.
