Summary auto-generated
This study investigates how Staphylococcus aureus recovers from nutrient starvation and resumes growth. Researchers starved S. aureus cells for 7 days in glucose-limited medium, then monitored their response to nutrient addition. Recovery required both glucose and amino acids together; either nutrient alone was insufficient. After nutrient addition, cells exhibited a lag period of 120-150 minutes before resuming division. During this lag, RNA synthesis increased immediately while protein synthesis was delayed by approximately 5 minutes. Cells enlarged within 30 minutes and initiated chromosome replication after 90 minutes. Protein expression profiles changed dramatically: starvation-specific proteins were rapidly downregulated within 30 minutes, while some proteins were expressed only during recovery. Importantly, protein synthesis continued even when RNA synthesis was inhibited, indicating that starved cells contain long-lived mRNA transcripts that persist and are translated during recovery. The recovery mechanism is independent of starvation duration and involves a coordinated sequence of molecular and physiological changes.
Key findings
- S. aureus requires both glucose and amino acids together to recover from starvation; either nutrient alone is insufficient
- Recovery involves a fixed 120-150 minute lag period before cell division, independent of starvation duration
- RNA synthesis increases immediately upon nutrient addition, while protein synthesis is delayed by 5 minutes
- Starved cells contain stable mRNA transcripts synthesized during starvation that are translated during recovery without requiring new RNA synthesis
- Specific starvation proteins are rapidly degraded during recovery while new recovery-specific proteins are transiently expressed in a temporal sequence
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Abstract
Nutrient limitation of Staphylococcus aureus induces a starvation- survival state which enables it to survive until sufficient nutrients become available to support growth. The response of starved S. aureus cells to nutritional upshift was analysed to characterize the recovery mechanism which results in the resumption of rapid growth. S. aureus 8325-4 starved for 7 d in a chemically defined medium limited for glucose was able to resume growth upon the addition of complex medium (brain heart infusion broth) or a mixture of amino acids and glucose. The addition of either glucose or amino acids alone did not lead to recovery of cells. Prior to the first cell division event, a lag period of about 120-150 min was observed, the duration of which was independent of the length of starvation survival. During this lag period, RNA synthesis increased immediately upon the addition of nutrients whilst protein synthesis was delayed by approximately 5 min. Cells rapidly enlarged within 30 min of recovery, and initiation of chromosome replication could be detected after 90 min. Changes in the profile of proteins expressed during the recovery period revealed that several starvation-specific proteins were down-regulated within 30 min, whilst other proteins were common to both starvation and recovery. Two proteins were identified which were only transiently expressed during the first 60 min of recovery. Protein synthesis could be detected during recovery even if the cells had been treated with the RNA synthesis inhibitor rifampicin for 30 min prior to the addition of recovery nutrients, demonstrating that several proteins are translated from long-lived mRNA transcripts present in starved cells.