tRNA modification landscapes in streptococci: shared losses and clade-specific adaptations

Area of Science:

• Microbiology
• Molecular Biology
• Genomics

Background:

• Transfer RNA (tRNA) modifications are essential for accurate and efficient protein synthesis in bacteria.
• Gram-positive pathogens like Streptococcus mutans and Streptococcus pneumoniae rely on tRNA modifications for translational control.
• Understanding these modifications is key to developing novel antimicrobial strategies.

Purpose of the Study:

• To comprehensively map tRNA modification genes in Streptococcus mutans and Streptococcus pneumoniae.
• To investigate species-specific variations in tRNA modification pathways.
• To elucidate the functional significance of tRNA modifications in bacterial pathogens.

Main Methods:

• Integration of genetics, mass spectrometry, epitranscriptomics, and comparative genomics.
• Analysis of tRNA modification pathways across 1599 sequenced streptococcal genomes.
• Comparative essentiality profiling of modification genes.

Main Results:

• Both species exhibit a reduction in modifications dependent on iron-sulfur (Fe-S) cluster enzymes.
• Specific modifications (D, m1A, m7G, t6A, i6A) were mapped in S. pneumoniae, with DusB1 identified as the sole enzyme for D modification.
• Distinct queuosine (Q) metabolism strategies were observed: S. mutans synthesizes Q de novo, while S. pneumoniae salvages preQ₁.
• The N⁶-threonylcarbamoyladenosine (t⁶A) synthesis enzyme TsaE is essential in S. pneumoniae but not S. mutans, with suppressor mutations in asnS restoring viability.

Conclusions:

• tRNA modification patterns differ significantly between S. mutans and S. pneumoniae, reflecting adaptations to their respective environments and metabolic strategies.
• The loss of Fe-S enzyme-dependent modifications is a conserved trend in Streptococcus species.
• tRNA modifications play a critical role in the recognition of tRNAs by aminoacyl-tRNA synthetases, impacting bacterial viability.