tRNA Modification Landscapes in Streptococci: Shared Losses and Clade-Specific Adaptations

Area of Science:

• Microbiology
• Molecular Biology
• Genomics

Background:

• Transfer RNA (tRNA) modifications are crucial for bacterial translational control and gene expression.
• Gram-positive pathogens like Streptococcus mutans and Streptococcus pneumoniae possess unique tRNA modification profiles.

Purpose of the Study:

• To comprehensively map tRNA modification genes in S. mutans and S. pneumoniae.
• To investigate the functional significance of these modifications and associated enzymes.
• To compare tRNA modification pathways across streptococcal species.

Main Methods:

• Genetics
• Mass spectrometry
• Epitranscriptomics
• Comparative genomics
• Essentiality profiling

Main Results:

• Both species exhibit reduced iron-sulfur enzyme-dependent tRNA modifications.
• Specific modifications (D, m1A, m7G, t6A, i6A) were mapped in S. pneumoniae, with DusB1 identified as the sole D modification enzyme.
• Distinct queuosine (Q) metabolism pathways were observed: S. mutans synthesizes Q de novo, while S. pneumoniae salvages preQ1.
• Comparative genomics revealed conserved Q metabolism strategies across 1,599 streptococcal genomes.
• The N-threonylcarbamoyladenosine (t6A) synthesis enzyme TsaE is essential in S. pneumoniae but not S. mutans.
• Suppressor mutations in asnS (encoding AsnRS) partially restored viability to ΔtsaE mutants.

Conclusions:

• tRNA modification patterns vary significantly between S. mutans and S. pneumoniae, reflecting adaptations in central metabolism and enzyme utilization.
• The study underscores the functional importance of tRNA modifications in aminoacyl-tRNA synthetase recognition and bacterial viability.
• Comparative analysis provides insights into the evolution and conservation of tRNA modification pathways within the Streptococcus genus.