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.


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