Time-resolved RNA-seq analysis to unravel the in vivo competence induction by Streptococcus pneumoniae during pneumonia-derived sepsis

Myung Whan Oh, Jingjun Lin, Sook Yin Chong, Shi Qian Lew, Tauqeer Alam, Gee W. Lau

Research output: Contribution to journalArticlepeer-review

Abstract

Competence development in Streptococcus pneumoniae (pneumococcus) is tightly intertwined with virulence. In addition to genes encoding genetic transformation machinery, the competence regulon also regulates the expression of allolytic factors, bacteriocins, and cytotoxins. Pneumococcal competence system has been extensively interrogated in vitro where the short transient competent state upregulates the expression of three distinct phases of “early,” “late,” and “delayed” genes. Recently, we have demonstrated that the pneumococcal competent state develops naturally in mouse models of pneumonia-derived sepsis. To unravel the underlying adaptive mechanisms driving the development of the competent state, we conducted a time-resolved transcriptomic analysis guided by the spatiotemporal live in vivo imaging system of competence induction during pneumonia-derived sepsis. Mouse lungs infected by the serotype 2 strain D39 expressing a competent state-specific reporter gene (D39-ssbB-luc) were subjected to RNA sequencing guided by monitoring the competence development at 0, 12, 24, and, at the moribund state, >40 hours post-infection (hpi). Transcriptomic analysis revealed that the competence-specific gene expression patterns in vivo were distinct from those under in vitro conditions. There was significant upregulation of early, late, and some delayed phase competence-specific genes as early as 12 hpi, suggesting that the pneumococcal competence regulon is important for adaptation to the lung environment. Additionally, members of the histidine triad (pht) gene family were sharply upregulated at 12 hpi followed by a steep decline throughout the rest of the infection cycle, suggesting that Pht proteins participate in the early adaptation to the lung environment. Further analysis revealed that Pht proteins execute a metal ion-dependent regulatory role in competence induction.

Original languageEnglish (US)
JournalMicrobiology Spectrum
Volume12
Issue number3
DOIs
StatePublished - Mar 2024

Keywords

  • KEYWORDS Streptococcus pneumoniae
  • Pht histidine triad proteins
  • RNA-seq
  • competent state
  • host adaptation
  • pneumonia-derived sepsis

ASJC Scopus subject areas

  • Physiology
  • Ecology
  • General Immunology and Microbiology
  • Genetics
  • Microbiology (medical)
  • Cell Biology
  • Infectious Diseases

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