Pivotal Roles for Ribonucleases in Streptococcus pneumoniae Pathogenesis

Area of Science:

• Microbiology
• Molecular Biology
• Bacterial Pathogenesis

Background:

• Bacterial RNases regulate gene expression and virulence.
• Streptococcus pneumoniae is a major human respiratory pathogen.
• The roles of RNase Y and PNPase in S. pneumoniae were previously uncharacterized.

Purpose of the Study:

• To investigate the impact of RNase Y and PNPase on S. pneumoniae physiology and virulence.
• To elucidate the transcriptomic changes induced by the absence of RNase Y and PNPase.

Main Methods:

• Deletion mutant construction for RNase Y (Δrny) and PNPase (Δpnp).
• Murine models of invasive pneumonia to assess virulence.
• Genome-wide transcriptomic analysis (RNA sequencing).

Main Results:

• Both Δrny and Δpnp mutants exhibited significantly attenuated virulence in vivo.
• Δrny mutant showed pleiotropic defects in cell morphology and growth, with altered expression of ~200 mRNAs and several small regulatory RNAs (sRNAs).
• Δpnp mutant displayed altered expression of 40 transcripts, including tryptophan biosynthesis genes and 5' cis-acting regulatory RNAs, without in vitro growth defects.

Conclusions:

• RNase Y plays a global role in pneumococcal physiology, affecting cell division, metabolism, stress response, and virulence.
• PNPase primarily mediates virulence phenotypes, likely through the regulation of sRNAs.
• Both RNases are crucial for S. pneumoniae pathogenesis, highlighting their potential as therapeutic targets.