Streptococcus pneumoniae Elaborates Persistent and Prolonged Competent State during Pneumonia-Derived Sepsis

Abstract

The competence regulon of pneumococcus regulates both genetic transformation and virulence. However, competence induction during host infection has not been examined. By using the serotype 2 strain D39, we transcriptionally fused the firefly luciferase (luc) to competence-specific genes and spatiotemporally monitored the competence development in a mouse model of pneumonia-derived sepsis. In contrast to the universally reported short transient burst of competent state in vitro, the naturally developed competent state was prolonged and persistent during pneumonia-derived sepsis. The competent state began at approximately 20 h postinfection (hpi) and facilitated systemic invasion and sepsis development and progressed in different manners. In some mice, acute pneumonia quickly led to sepsis and death, accompanied by increasing intensity of the competence signal. In the remaining mice, pneumonia lasted longer, with the competence signal decreasing at first but increasing as the infection became septic. The concentration of pneumococcal inoculum (1 × 106 to 1 × 108 CFU/mouse) and postinfection lung bacterial burden did not appreciably impact the kinetics of competence induction. Exogenously provided competence stimulating peptide 1 (CSP1) failed to modulate the onset kinetics of competence development in vivo. The competence shutoff regulator DprA was highly expressed during pneumonia-derived sepsis but failed to turn off the competent state in mice. Competent D39 bacteria propagated the competence signal through cell-to-cell contact rather than the classically described quorum-sensing mechanism. Finally, clinical pneumococcal strains of different serotypes were also able to develop natural competence during pneumonia-derived sepsis.

Colonization of the Murine Oropharynx by Streptococcus pyogenes Is Governed by the Rgg2/3 Quorum Sensing System

“…3) indicates that the environment of the nasopharynx overrides any potential products that pre-conditioning produces during activation of the QS circuit. On a similar note, it was recently shown that although the competence quorum sensing system in S. pneumoniae is activated in the murine respiratory tract, addition of activating CSP peptide pheromone was unable to induce competence in vivo [38].…”

Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole animal dual RNA-seq

“…5A). It also challenges the idea that competence is constitutively expressed by individual bacteria in the host (Lin et al, 2020), but rather that there are pockets of pneumococci inducing competence during infection (Fig. 5).…”

Competence remodels the pneumococcal cell wall providing resistance to fratricide and surface exposing key virulence factors

“…In addition, competence is also activated when cells are adhering to human epithelial cells (Aprianto et al, 2016), and during invasive disease as shown in several mouse and zebrafish models (Lin et al, 2020; Schmidt et al, 2019)(Jim et al, 2022). Indeed, competence development is a key pathogenic factor in pneumococcal meningitis (Jim et al, 2022; Schmidt et al, 2019).…”