Flores-Kim, J. orcid.org/0000-0001-8282-6647, Dobihal, G.S., Fenton, A. orcid.org/0000-0003-4042-4580 et al. (2 more authors) (2019) A switch in surface polymer biogenesis triggers growth-phase-dependent and antibiotic-induced bacteriolysis. eLife, 8. e44912. ISSN 2050-084X
Abstract
Penicillin and related antibiotics disrupt cell wall synthesis to induce bacteriolysis. Lysis in response to these drugs requires the activity of cell wall hydrolases called autolysins, but how penicillins misactivate these deadly enzymes has long remained unclear. Here, we show that alterations in surface polymers called teichoic acids (TAs) play a key role in penicillin-induced lysis of the Gram-positive pathogen Streptococcus pneumoniae (Sp). We find that during exponential growth, Sp cells primarily produce lipid-anchored TAs called lipoteichoic acids (LTAs) that bind and sequester the major autolysin LytA. However, penicillin-treatment or prolonged stationary phase growth triggers the degradation of a key LTA synthase, causing a switch to the production of wall-anchored TAs (WTAs). This change allows LytA to associate with and degrade its cell wall substrate, thus promoting osmotic lysis. Similar changes in surface polymer assembly may underlie the mechanism of antibiotic- and/or growth phase-induced lysis for other important Gram-positive pathogens.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, Flores-Kim et al. This article is distributed under the terms of the Creative Commons Attribution License, http://creativecommons.org/licenses/by/4.0/ which permits unrestricted use and redistribution provided that the original author and source are credited. |
Keywords: | S. pneumoniae; antibiotics; cell wall; infectious disease; microbiology; peptidoglycan; teichoic acid |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Molecular Biology and Biotechnology (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 29 Apr 2019 10:27 |
Last Modified: | 29 Apr 2019 22:17 |
Status: | Published |
Publisher: | eLife Sciences Publications |
Refereed: | Yes |
Identification Number: | 10.7554/eLife.44912 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:145110 |