Competence remodels the pneumococcal cell wall exposing key surface virulence factors that mediate increased host adherence

Minhas, Vikrant and Domenech, Arnau and Synefiaridou, Dimitra and Straume, Daniel and Brendel, Max and Cebrero, Gonzalo and Liu, Xue and Costa, Charlotte and Baldry, Mara and Sirard, Jean-Claude and Perez, Camilo and Gisch, Nicolas and Hammerschmidt, Sven and Håvarstein, Leiv Sigve and Veening, Jan-Willem. (2023) Competence remodels the pneumococcal cell wall exposing key surface virulence factors that mediate increased host adherence. PLoS Biology, 21 (1). e3001990.

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Official URL: https://edoc.unibas.ch/93773/

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Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation, and virulence. Competent bacteria produce so-called "fratricins" such as CbpD that kill noncompetent siblings by cleaving peptidoglycan (PGN). CbpD is a choline-binding protein (CBP) that binds to phosphorylcholine residues found on wall and lipoteichoic acids (WTA and LTA) that together with PGN are major constituents of the pneumococcal cell wall. Competent pneumococci are protected against fratricide by producing the immunity protein ComM. How competence and fratricide contribute to virulence is unknown. Here, using a genome-wide CRISPRi-seq screen, we show that genes involved in teichoic acid (TA) biosynthesis are essential during competence. We demonstrate that LytR is the major enzyme mediating the final step in WTA formation, and that, together with ComM, is essential for immunity against CbpD. Importantly, we show that key virulence factors PspA and PspC become more surface-exposed at midcell during competence, in a CbpD-dependent manner. Together, our work supports a model in which activation of competence is crucial for host adherence by increased surface exposure of its various CBPs.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology (Perez)
UniBasel Contributors:Perez, Camilo and Cebrero, Gonzalo Felipe
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Public Library of Science
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:28 Feb 2023 11:42
Deposited On:28 Feb 2023 11:42

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