StIA is a Novel Nucleoid-Associated Protein of Streptococcus pneumoniae that Activates DNA Topoisomerase I

A newly discovered protein, named StIA, is found in Streptococcus pneumoniae, a human pathogen responsible for causing infections. This protein, which binds to DNA in a non-specific manner, plays a role in regulating the activity of topoisomerase I (Topo I), an enzyme essential for maintaining DNA topology. StIA was given this name as it specifically activates Topo I. When StIA is overproduced, the bacteria become less susceptible to Topo I inhibitors, and its deletion results in impaired growth of the bacteria in the presence of such inhibitors.

The researchers found that StIA forms oligomers and assembles into higher-order nucleoprotein complexes when bound to DNA. This protein does not affect DNA cleavage by Topo I but instead enhances the DNA religation step of its catalytic cycle. This activation is likely due to a direct protein-protein interaction between StIA and Topo I. Structural modeling of the interaction suggests that StIA and Topo I physically associate and identifies specific contact residues involved in the interaction.

The findings highlight StIA as a novel nucleoid-associated protein with dual functions: promoting nucleoprotein complex assembly and stimulating Topo I activity through direct interaction with the enzyme. This regulation of topoisomerase activity by accessory proteins could be an important mechanism for fine-tuning DNA topological homeostasis, which could potentially lead to new strategies in developing antibacterial therapies.