@article{TEXTUAL,
      recid = {10334},
      author = {Ibrahim, Amany M. and Azam, Muhammad S. and Schneewind,  Olaf and Missiakas, Dominique},
      title = {Processing of LtaS restricts LTA assembly and YSIRK  preprotein trafficking into <i>Staphylococcus  aureus</i> cross-walls},
      journal = {mBio},
      address = {2024-01-04},
      number = {TEXTUAL},
      abstract = {Septal membranes of Staphylococcus aureus serve as the  site of secretion for precursors endowed with the YSIRK  motif. Depletion of ltaS, a gene required for lipoteichoic  acid (LTA) synthesis, results in the loss of restricted  trafficking of YSIRK precursors to septal membranes. Here,  we seek to understand the mechanism that ties LTA assembly  and trafficking of YSIRK precursors. We confirm that  catalytically inactive lipoteichoic acid synthase  (LtaS)<sub>T300A</sub> does not support YSIRK precursor  trafficking to septa. We hypothesize that the enzyme’s  reactants [gentiobiosyldiacylglycerol (Glc<sub>2</sub>-DAG)  and phosphatidylglycerol (PG)] or products [LTA and  diacylglycerol (DAG)], not LtaS, must drive this process.  Indeed, we observe that septal secretion of the  staphylococcal protein A YSIRK precursor is lost in ypfP  and ltaA mutants that produce glycerophosphate polymers  [poly(Gro-P)] without the Glc<sub>2</sub>-DAG lipid anchor.  These mutants display longer poly(Gro-P) chains, implying  enhanced PG consumption and DAG production. Our experiments  also reveal that in the absence of Glc<sub>2</sub>-DAG, the  processing of LtaS to the extracellular catalytic domain,  eLtaS, is impaired. Conversely, LTA polymerization is  delayed in a strain producing LtaSS<sub>218P</sub>, a  variant processed more slowly than LtaS. We conclude that  Glc<sub>2</sub>-DAG binding to the enzyme couples catalysis  by LtaS and the physical release of eLtaS. We propose a  model for the temporal and localized assembly of LTA into  cross-walls. When LtaS is not processed in a timely manner,  eLtaS no longer diffuses upon daughter cell splitting, LTA  assembly continues, and the unique septal-lipid pool, PG  over DAG ratio, is not established. This results in  profound physiological changes in S. aureus cells,  including the inability to restrict the secretion of YSIRK  precursors at septal membranes.},
      url = {http://knowledge.uchicago.edu/record/10334},
}