Lytic transglycosylases mitigate periplasmic crowding by degrading soluble cell wall turnover products
- Cornell University, United States
- Umeå University, Sweden
- Indiana University, United States
Abstract
The peptidoglycan cell wall is a predominant structure of bacteria, determining cell shape and supporting survival in diverse conditions. Peptidoglycan is dynamic and requires regulated synthesis of new material, remodeling, and turnover - or autolysis - of old material. Despite exploitation of peptidoglycan synthesis as an antibiotic target, we lack a fundamental understanding of how peptidoglycan synthesis and autolysis intersect to maintain the cell wall. Here, we uncover a critical physiological role for a widely misunderstood class of autolytic enzymes, lytic transglycosylases (LTGs). We demonstrate that LTG activity is essential to survival by contributing to periplasmic processes upstream and independent of peptidoglycan recycling. Defects accumulate in Vibrio cholerae LTG mutants due to generally inadequate LTG activity, rather than absence of specific enzymes, and essential LTG activities are likely independent of protein-protein interactions, as heterologous expression of a non-native LTG rescues growth of a conditionally LTG-null mutant. Lastly, we demonstrate that soluble, uncrosslinked, endopeptidase-dependent peptidoglycan chains, also detected in the wild-type, are enriched in LTG mutants, and that LTG mutants are hypersusceptible to the production of diverse periplasmic polymers. Collectively, our results suggest that LTGs prevent toxic crowding of the periplasm with synthesis-derived peptidoglycan polymers and contrary to prevailing models, that this autolytic function can be temporally separate from peptidoglycan synthesis.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figures 1 and 3.
Article and author information
Author details
Anna Isabell Weaver
Funding
National Institutes of Health (R01-GM130971)
- Tobias Dörr
Molecular Infection Medicine Sweden (MIMS2012)
- Felipe Cava
Knut and Alice Wallenberg Foundation (KAW2012.0184)
- Felipe Cava
Swedish Research Council (VR2018-02823)
- Felipe Cava
Kempe Foundation (SMK2062)
- Felipe Cava
National Institutes of Health (R01-GM113172)
- Michael S vanNieuwenhze
National Institutes of Health (R35-GM136365)
- Michael S vanNieuwenhze
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Weaver 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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Lytic transglycosylases mitigate periplasmic crowding by degrading soluble cell wall turnover products
eLife 11:e73178.
https://doi.org/10.7554/eLife.73178
