ABSTRACT The role of chromosomally encoded toxin-antitoxin (TA) loci in bacterial physiology has been under debate, with the toxin proposed as either an inducer of bacteriostasis or a mediator of programmed cell death (PCD). We report here that ectopic expression of MazF _Sa , a toxin of the TA module from Staphylococcus aureus , led to a rapid decrease in CFU counts but most cells remained viable as determined by differential Syto 9 and propidium iodide staining after MazF _Sa induction. This finding suggested that the toxin MazF _Sa induced cell stasis rather than cell death. We also showed that MazF _Sa selectively cleaves cellular mRNAs in vivo, avoiding “important” transcripts such as recA , gyrB , and sarA mRNAs in MazF _Sa -induced cells, while these three mRNAs can be cleaved in vitro. The results of Northwestern blotting showed that both sarA and recA mRNAs bind strongly to a putative RNA-binding protein. These data suggest that S. aureus likely undergoes stasis by protecting selective mRNA with RNA-binding proteins upon the expression of MazF _Sa in vivo.