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

Author:

Minhas VikrantORCID,Domenech ArnauORCID,Synefiaridou DimitraORCID,Straume DanielORCID,Brendel Max,Cebrero GonzaloORCID,Liu XueORCID,Costa CharlotteORCID,Baldry MaraORCID,Sirard Jean-ClaudeORCID,Perez CamiloORCID,Gisch NicolasORCID,Hammerschmidt SvenORCID,Håvarstein Leiv SigveORCID,Veening Jan-WillemORCID

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.

Funder

Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung

HORIZON EUROPE European Research Council

Deutsche Forschungsgemeinschaft

Helmut Horten Stiftung

Publisher

Public Library of Science (PLoS)

Subject

General Agricultural and Biological Sciences,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Neuroscience

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