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Type II (proteic) chromosomal toxin-antitoxin systems (TAS) are widespread in Bacteria and Archaea but their precise function is known only for a limited number of them. Out of the many TAS described, the  relBE  family is one of the most abundant, being present in the three first sequenced strains of  Streptococcus pneumoniae  (D39, TIGR4 and R6). To address the function of the pneumococcal  relBE2Spn  TAS in the bacterial physiology, we have compared the response of the R6- relBE2Spn  wild type strain with that of an isogenic derivative, Δ relB2Spn  under different stress conditions such as carbon and amino acid starvation and antibiotic exposure. Differences on viability between the wild type and mutant strains were found only when treatment directly impaired protein synthesis. As a criterion for the permanence of this locus in a variety of clinical strains, we checked whether the  relBE2Spn  locus was conserved in around 100 pneumococcal strains, including clinical isolates and strains with known genomes. All strains, although having various types of polymorphisms at the vicinity of the TA region, contained a functional  relBE2Spn  locus and the type of its structure correlated with the multilocus sequence type. Functionality of this TAS was maintained even in cases where severe rearrangements around the  relBE2Spn  region were found. We conclude that even though the  relBE2Spn  TAS is not essential for pneumococcus, it may provide additional advantages to the bacteria for colonization and/or infection.

The relBE2Spn Toxin-Antitoxin System of Streptococcus pneumoniae: Role in Antibiotic Tolerance and Functional Conservation in Clinical Isolates