Ribo-seq reveals IsrR-mediated translational repression of SAOUHSC_02924 (gabT) during iron limitation in Staphylococcus aureus

Abstract

Iron is essential for bacterial growth but can be toxic in excess. To maintain iron homeostasis, bacteria employ regulatory mechanisms, including small RNAs (sRNAs). In Staphylococcus aureus, we identified the sRNA IsrR as a critical mediator of the iron-sparing response, enabling bacterial fitness in iron-limited environments such as those encountered during host infection. Here, we use ribosome profiling (Ribo-seq) to define the translational regulatory network of IsrR under iron-limited conditions. Our analysis identifies multiple genes under IsrR control, including SAOUHSC_02924 (gabT), which encodes a putative 4-aminobutyrate aminotransferase. Given that IsrR downregulates iron-dependent TCA cycle enzymes, we propose that repression of gabT prevents the accumulation of TCA cycle precursors under iron depletion, thereby avoiding metabolic imbalances. These findings expand the role of IsrR in metabolic reprogramming and highlight its contribution to S. aureus survival in iron-restricted host niches.