Peptidoglycan precursor synthesis along the sidewall of pole-growing mycobacteria
- University of Massachusetts, United States
- Central Michigan University, United States
- Harvard Medical School, United States
- Harvard TH Chan School of Public Health, United States
Abstract
Rod-shaped mycobacteria expand from their poles, yet d-amino acid probes label cell wall peptidoglycan in this genus at both the poles and sidewall. We sought to clarify the metabolic fates of these probes. Monopeptide incorporation was decreased by antibiotics that block peptidoglycan synthesis or l,d-transpeptidation and in an l,d-transpeptidase mutant. Dipeptides complemented defects in d-alanine synthesis or ligation and were present in lipid-linked peptidoglycan precursors. Characterizing probe uptake pathways allowed us to localize peptidoglycan metabolism with precision: monopeptide-marked l,d-transpeptidase remodeling and dipeptide-marked synthesis were coincident with mycomembrane metabolism at the poles, septum and sidewall. Fluorescent pencillin-marked d,d-transpeptidation around the cell perimeter further suggested that the mycobacterial sidewall is a site of cell wall assembly. While polar peptidoglycan synthesis was associated with cell elongation, sidewall synthesis responded to cell wall damage. Peptidoglycan editing along the sidewall may support cell wall robustness in pole-growing mycobacteria.
Data availability
Source data has been provided with manuscript submission. These data will be deposited to Open Science Framework prior to publication.
Article and author information
Author details
Alam García-Heredia
Funding
National Institutes of Health (New Innovator Award DP2 AI138238)
- M Sloan Siegrist
National Science Foundation (CAREER 1654408)
- Benjamin M Swarts
Simons Foundation (Life Sciences Research Foundation Fellowship)
- Hoong Chuin Lim
Research Corporation for Science Advancement (Cottrell College Science Award 22525)
- Benjamin M Swarts
National Institutes of Health (U01CA221230)
- M Sloan Siegrist
National Institutes of Health (Training Grant T32 GM008515)
- Emily S Melzer
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, García-Heredia 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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Peptidoglycan precursor synthesis along the sidewall of pole-growing mycobacteria
eLife 7:e37243.
https://doi.org/10.7554/eLife.37243
Further reading
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
A better understanding of the mechanisms underpinning the growth of mycobacteria could help identify targets for new antibiotics.
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- Biochemistry and Chemical Biology
- Structural Biology and Molecular Biophysics
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