Discovery of the role of a SLOG superfamily biological conflict systems associated protein IodA (YpsA) in oxidative stress protection and cell division inhibition in Gram-positive bacteria

Abstract

Bacteria adapt to different environments by regulating cell division and several conditions that modulate cell division have been documented. Understanding how bacteria transduce environmental signals to control cell division is critical to comprehend the global network of cell division regulation. In this article we describe a role for Bacillus subtilis YpsA, an uncharacterized protein of the SLOG superfamily of nucleotide and ligand-binding proteins, in cell division. We observed that YpsA provides protection against oxidative stress as cells lacking ypsA show increased susceptibility to hydrogen peroxide treatment. We found that increased expression of ypsA leads to cell division inhibition due to defective assembly of FtsZ, the tubulin-like essential protein that marks the sites of cell division. We showed that cell division inhibition by YpsA is linked to glucose availability. We generated YpsA mutants that are no longer able to inhibit cell division. Finally, we show that the role of YpsA is possibly conserved in Firmicutes, as overproduction of YpsA in Staphylococcus aureus also impairs cell division. Therefore, we propose ypsA to be renamed as iodA for inhibitor of division.\n\nIMPORTANCEAlthough key players of cell division in bacteria have been largely characterized, the factors that regulate these division proteins are still being discovered and evidence for the presence of yet-to-be discovered factors has been accumulating. How bacteria sense the availability of nutrients and how that information is used to regulate cell division positively or negatively is less well-understood even though some examples exist in the literature. We discovered that a protein of hitherto unknown function belonging to the SLOG superfamily of nucleotide/ligand-binding proteins, YpsA, influences cell division in Bacillus subtilis by integrating metabolic status such as the availability of glucose. We showed that YpsA is important for oxidative stress response in B. subtilis. Furthermore, we provide evidence that cell division inhibition function of YpsA is also conserved in another Firmicute Staphylococcus aureus. This first report on the role of YpsA (IodA) brings us a step closer in understanding the complete tool set that bacteria have at their disposal to regulate cell division precisely to adapt to varying environmental conditions.