Signal peptides direct surface proteins to two distinct envelope locations of Staphylococcus aureus

Abstract

Surface proteins of Gram‐positive bacteria are covalently linked to the cell wall envelope by a mechanism requiring an N‐terminal signal peptide and a C‐terminal LPXTG motif sorting signal. We show here that surface proteins of Staphylococcus aureus arrive at two distinct destinations in the bacterial envelope, either distributed as a ring surrounding each cell or as discrete assembly sites. Proteins with ring‐like distribution (clumping factor A (ClfA), Spa, fibronectin‐binding protein B (FnbpB), serine‐aspartate repeat protein C (SdrC) and SdrD) harbour signal peptides with a YSIRK/GS motif, whereas proteins directed to discrete assembly sites (S. aureus surface protein A (SasA), SasD, SasF and SasK) do not. Reciprocal exchange of signal peptides between surface proteins with (ClfA) or without the YSIRK/GS motif (SasF) directed recombinant products to the alternate destination, whereas mutations that altered only the YSIRK sequence had no effect. Our observations suggest that S. aureus distinguishes between signal peptides to address proteins to either the cell pole (signal peptides without YSIRK/GS) or the cross wall, the peptidoglycan layer that forms during cell division to separate new daughter cells (signal peptides with YISRK/GS motif).

Antiinfective therapy with a small molecule inhibitor of Staphylococcus aureus sortase

“…During bacterial growth, sortase catalyzes the assembly of surface proteins into the cell wall at the septal and polar compartments of S. aureus (25). Sortase-mediated cleavage of surface protein sorting signals can be measured with pulse-chase experiments, which permit an analysis of precursor processing using [ 35 S]Met/Cys radiolabeling of staphylococcal proteins and immunoprecipitation (26).…”

Mechanism for Sortase Localization and the Role of Sortase Localization in Efficient Pilus Assembly in Enterococcus faecalis

“…In the second model, domains within the secreted proteins themselves, and not the location of the Sec machinery, are proposed to direct the localization of secreted proteins in gram-positive cocci. A domain of the N-terminal secretion signal was shown to differentially influence the sites of protein F and M protein appearance on the cell surface of S. pyogenes, as well as that of a number of LPXTG-containing proteins in S. aureus (5,7). Consistent with the model for localized secretion machinery, Sec components were found to localize in a helical pattern along the lengths of both gram-positive B. subtilis and gram-negative E. coli rods (3,43), suggesting that secretion localization may be a conserved phenomenon in similarly shaped bacteria.…”

Peptidoglycan architecture can specify division planes in Staphylococcus aureus

“…Dynamic environmental conditions, such as those encountered during pathogenesis, will lead to alterations in surface protein expression. Th us, cells may also inherit a surface protein complement with heterogeneity within the population, especially of those proteins only attached during septum formation 32,33 . Such population-wide heterogeneity may provide a selective advantage in the ever-changing complex interaction between pathogen and host.…”