Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase
- Yale University School of Medicine, United States
Abstract
Typhoid toxin is a virulence factor for the bacterial pathogen Salmonella Typhi, which causes typhoid fever in humans. After its synthesis by intracellular bacteria, typhoid toxin is secreted into the lumen of the Salmonella-containing vacuole by a secretion mechanism strictly dependent on TtsA, a specific muramidase that facilitates toxin transport through the peptidoglycan layer. Here we show that substrate recognition by TtsA depends on a discrete domain within its carboxy terminus, which targets the enzyme to the bacterial poles to recognize YcbB-edited peptidoglycan. Comparison of the atomic structures of TtsA bound to its substrate and that of a close homolog with different specificity identified specific determinants involved in substrate recognition. Combined with structure-guided mutagenesis and in vitro and in vivo crosslinking experiments, this study provides an unprecedented view of the mechanisms by which a muramidase recognizes its peptidoglycan substrate to facilitate protein secretion.
Data availability
The diffraction data have been deposited in PDB under accession code 6v40 and 6v3z. The rest of the data are included in the manuscript and associated supporting files.
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Funding
National Institute of Allergy and Infectious Diseases (AI079022)
- Jorge E Galán
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2020, Geiger 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.
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Mechanisms of substrate recognition by a typhoid toxin secretion-associated muramidase
eLife 9:e53473.
https://doi.org/10.7554/eLife.53473
