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- Title
Competence remodels the pneumococcal cell wall exposing key surface virulence factors that mediate increased host adherence.
- Authors
Minhas, Vikrant; Domenech, Arnau; Synefiaridou, Dimitra; Straume, Daniel; Brendel, Max; Cebrero, Gonzalo; Liu, Xue; Costa, Charlotte; Baldry, Mara; Sirard, Jean-Claude; Perez, Camilo; Gisch, Nicolas; Hammerschmidt, Sven; Håvarstein, Leiv Sigve; Veening, Jan-Willem
- Abstract
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. Competence development in the human pathogen Streptococcus pneumoniae controls several features such as genetic transformation, biofilm formation and virulence. This study shows that competence activation is crucial for optimal host adherence, via a mechanism dependent on the fratricin CbpD, which exposes virulence factors to the cell surface.
- Subjects
GENETIC transformation; STREPTOCOCCUS pneumoniae; LIPOTEICHOIC acid; BIOSYNTHESIS; BIOFILMS
- Publication
PLoS Biology, 2023, Vol 21, Issue 1, p1
- ISSN
1544-9173
- Publication type
Article
- DOI
10.1371/journal.pbio.3001990