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

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.

Pneumococcal competence, a populational health sensor driving multilevel heterogeneity in response to antibiotics

“…Competence-mediated diversification of a clonal pneumococcal population may provide the best opportunity for survival in such environments. This idea is strengthened by the links between pneumococcal competence and virulence 18,20,22,63 , and the suggestion that a single cell bottleneck is at the origin of pneumococcal bacteraemia 64 .…”

“…Competence-mediated diversification of a clonal pneumococcal population may provide the best opportunity for survival in such environments. This idea is strengthened by the links between pneumococcal competence and virulence 18,20,22,63 , and the suggestion that a single cell bottleneck is at the origin of pneumococcal bacteraemia 64 . This study reveals that pneumococcal competence is a health sensor responding to phenotypic heterogeneity and proceeding via an SI&P mode in the face of environmental stresses (Figure 5F).…”

“…In addition, other properties are linked to competence, with the links undefined molecularly but important for the lifestyle of this pathogen in its human host. These include biofilm formation 16,17 , virulence [18][19][20][21][22] , increased survival upon transient antibiotic exposure 23 and host transmission 24 .…”

Transcriptional regulation of TacL-mediated lipoteichoic acids biosynthesis by ComE during competence impacts pneumococcal transformation

“…Bacterial surface polysaccharides also influence transformation capacity ( Weiser and Kapoor, 1999 ; Li et al., 2019 ; Minhas et al., 2023 ). For example, the pneumococcal cell envelope that is primarily composed of capsular polysaccharides (CPS) may impede DNA uptake and hence influence transformation ( Weiser and Kapoor, 1999 ).…”

“…Non-encapsulated strains demonstrate a higher level of transformability than encapsulated counterparts ( Ottolenghi and Macleod, 1963 ). Teichoic acids (TAs) have also been associated with bacterial transformation, as the transparent phenotype, characterized by elevated TAs and reduced CPS levels and it exhibits enhanced transformation efficiency compared to the opaque phenotype ( Weiser et al., 1994 ; Li et al., 2019 ; Minhas et al., 2023 ). Additionally, the deletion of licD2 , which leads to a reduction of phosphocholine modification in TAs, significantly decreases pneumococcal transformation ( Zhang et al., 1999 ).…”