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

PLoS Biol. 2023 Jan 30;21(1):e3001990. doi: 10.1371/journal.pbio.3001990. eCollection 2023 Jan.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / metabolism
  • Cell Wall / metabolism
  • Choline / metabolism
  • Humans
  • N-Acetylmuramoyl-L-alanine Amidase / chemistry
  • N-Acetylmuramoyl-L-alanine Amidase / genetics
  • N-Acetylmuramoyl-L-alanine Amidase / metabolism
  • Streptococcus pneumoniae* / genetics
  • Virulence Factors* / genetics
  • Virulence Factors* / metabolism

Substances

  • Virulence Factors
  • N-Acetylmuramoyl-L-alanine Amidase
  • Choline
  • Bacterial Proteins

Grants and funding

Work in the Veening lab is supported by the Swiss National Science Foundation (SNSF) (project grants 310030_200792 and 310030_192517 to JWV), SNSF JPIAMR grant (40AR40_185533 to JWV), SNSF NCCR ‘AntiResist’ (51NF40_180541 to JWV) and ERC consolidator grant 771534-PneumoCaTChER to JWV. This work was further supported by grants of the Deutsche Forschungsgemeinschaft (GI 979/1-2 to NG, HA 3125/5-2 to SH). Work in the Perez lab is supported by the SNSF (PP00P3_198903 to CP) and the Helmut Horten Stiftung (HHS to CP) grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.