Surface proteins play a critical role in the pathogenesis and survival of Gram-positive bacteria in an infected host. Anchoring of surface proteins to the cell wall is highly regulated in both space and time, and is coordinated with cell division. Newly synthesized surface proteins contain an N-terminal signal sequence that targets them for secretion across the membrane. Depending on the type of signal sequence, proteins are translocated either at the septum or cell periphery, resulting in distinct cellular distribution patterns. The C-terminus of surface proteins contain a cell wall sorting signal (CWS), composed of an LPXTG motif, a hydrophobic stretch, and a few positive amino acids. Translocation of surface proteins stalls when the CWS reaches the secretion channel, leaving the LPXTG motif exposed outside the membrane. This motif is then cleaved by the enzyme sortase, and covalently attached to lipid II, leading to cell wall anchoring. Sortase is dynamically localized to membranal foci that are primarily associated with the division septum, and is recruited to the septum at an early stage. In this chapter, we review the spatial regulation of surface anchoring in Streptococcus pyogenes and how it relates to protein secretion and cell division.
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